Advertisement

Genetic Manipulation of Mammary Gland Development and Lactation

  • Darryl L. Hadsell
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 554)

Abstract

The mammalian genome is believed to contain some 30,000 to 40,000 different genes. Of these an estimated 42% have no known function. Genetically engineered mouse models (GEMM) have been a powerful tool available for determining gene function in vivo. In the mammary gland, a variety of genetic engineering approaches have been applied successfully to understanding the importance of specific gene products to mammary gland development and lactation. Our own laboratory has applied genetically engineered mice to facilitate understanding of the regulation of mammary gland development and lactation by insulin-like growth factors (IGF) and by the transcription factor, upstream stimulatory factor (USF-2). Our studies on transgenic mice that overexpress IGF-I have demonstrated the importance of IGF-dependent signaling pathways to maintenance of mammary epithelial cells during the declining phase of lactation. Our analysis of early developmental processes in mammary tissue from mice that carry a targeted mutation in the IGF-I receptor gene suggests that IGF-dependent stimulation of cell cycle progression is more important to early mammary gland development than potential antiapoptotic effects. Lastly, our studies on mice that carry a targeted mutation of the Usf2 gene have demonstrated that this gene is necessary for normal lactation and have highlighted the importance of this gene to the maintenance of protein synthesis. These studies, as well as studies of others, have highlighted both the strengths and limitations inherent in the use of GEMM. Limitations serve as the driving force behind development of new experimental strategies and genetic engineering schemes that will allow for a full understanding of gene function within the mammary gland.

Keywords

Mammary Gland Milk Yield Mouse Mammary Tumor Virus Mammary Gland Development Upstream Stimulatory Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Accili D, Drago J, Lee EJ, Johnson MD, Cool MH, Salvatore P, Asico LD, Jose PA, Taylor SI, Westphal H. Early neonatal death in mice homozygous for a null allele of the insulin receptor gene. Nat Genet 1996;12:106–109.PubMedCrossRefGoogle Scholar
  2. Ackler S, Ahmad S, Tobias C, Johnson MD, Glazer RI. Delayed mammary gland involution in mmtv-aktl transgenic mice. Oncogene 2002;21:198–206.PubMedCrossRefGoogle Scholar
  3. Adam D. Draft cow genome heads the field. Nature 2002;417:778.PubMedCrossRefGoogle Scholar
  4. Andres AC, Schonenberger CA, Groner B, Hennighausen L, LeMeur M, Gerlinger P. Ha-ras oncogene expression directed by a milk protein gene promoter: tissue specificity, hormonal regulation, and tumor induction in transgenic mice. Proc Natl Acad Sci USA 1987;84:1299–1303.PubMedCrossRefGoogle Scholar
  5. Araki E, Lipes MA, Patti ME, Bruning JC, Haag B, Johnson RS, Kahn CR. Alternative pathway of insulin signalling in mice with targeted disruption of the IRS-1 gene. Nature 1994;372:186–190.PubMedCrossRefGoogle Scholar
  6. Arranz JJ, Coppieters W, Berzi P, Cambisano N, Grisart B, Karim L, Marcq F, Moreau L, Mezer C, Riquet J, Simon P, Vanmanshoven P, Wagenaar D, Georges M. A QTL affecting milk yield and composition maps to bovine chromosome 20: a confirmation. Anim Genet 1998;29:107–115.PubMedCrossRefGoogle Scholar
  7. Baker J, Liu J-P, Robertson E, Efstratiadis A. Role of insulin-like growth factors in embryonic and postnatal growth. Cell 1997;75:73–82.Google Scholar
  8. Bates P, Fisher R, Ward A, Richardson L, Hill DJ, Graham CF. Mammary cancer in transgenic mice expressing insulin-like growth factor II (IGF-II). BrJCancer 1996;72:1189–1193.Google Scholar
  9. Bendali AJ, Molloy PL. Base preferences for DNA binding by the bHLH-Zip protein USF: effects of MgC12 on specificity and comparison with binding of Myc family members. Nucleic Acids Res 1994;22:2801–2810.CrossRefGoogle Scholar
  10. Blackwell TK, Kretzner L, Blackwood EM, Eisenman RN, Weintraub H. Sequence-specific DNA binding by the c-myc protein. Science 1990;250:1149–1151.PubMedCrossRefGoogle Scholar
  11. Bohula EA, Salisbury AJ, Sohail M, Playford MP, Riedemann J, Southern EM, Macaulay VM. The efficacy of small interfering RNAs targeted to the type 1 insulin-like growth factor receptor (IGF1R) is influenced by secondary structure in the IGF1R transcript. J Biol Chem 2003;278:15991–15997.PubMedCrossRefGoogle Scholar
  12. Bonnette SG, Hadsell DL. Targeted disruption of the insulin-like growth factor I receptor gene inhibits cellular proliferation in mammary terminal endbuds (TEB). Endocrinology 2001;142:4937–4945.PubMedCrossRefGoogle Scholar
  13. Bremel RD, Yom HC, Bleck GT. Alteration of milk composition using molecular genetics. J Dairy Sci 1989;72:2826–2833.PubMedCrossRefGoogle Scholar
  14. Brinster RL, Chen HY, Messing A, Van Dyke T, Levine AJ, Palmiter RD. Transgenic mice harboring SV40 T-antigen genes develop characteristic brain tumors. Cell 1984;37:367–379.PubMedCrossRefGoogle Scholar
  15. Burks DJ, Font de Mora J, Schubert M, Withers DJ, Myers MG, Towery HH, Altamuro SL, Flint CL, White MF. IRS-2 pathways integrate female reproduction and energy homeostasis. Nature 2000;407:377–382.PubMedCrossRefGoogle Scholar
  16. Burrin DG, Fiorotto ML, Hadsell DL. Transgenic hypersecretion of des(l-3)human insulin-like growth factor I in mouse milk has limited effects on the gastrointestinal tract in suckling pups. J Nutr 1999; 129;51–56.PubMedGoogle Scholar
  17. Butte NF, Garza C, Smith EO, Nichols BL. Human milk intake and growth in exclusively breast-fed infants. J Pediatr 1984;104:187–195.PubMedCrossRefGoogle Scholar
  18. Byrne GW, Ruddle FH Multiplex gene regulation: a two-tiered approach to transgene regulation in transgenic mice. Proc Natl Acad Sci USA 1989;86:5473–5477.PubMedCrossRefGoogle Scholar
  19. Capuco AV, Kahl S, Jack LJ, Bishop JO, Wallace H. Prolactin and growth hormone stimulation of lactation in mice requires thyroid hormones. Proc Soc Exp Biol Med 1999;221:345–351.PubMedCrossRefGoogle Scholar
  20. Carmell MA, Zhang L, Conklin D, Harmon GJ, Rosenquist TA. Germline transmission of RNAi in mice. Nat Struct Biol 2003;10:91–92.PubMedCrossRefGoogle Scholar
  21. Chapman RS, Lourenco P, Tonner E, Flint D, Selbert S, Takeda K, Akira S, Clarke AR, Watson CJ. The role of Stat3 in apoptosis and mammary gland involution. Conditional deletion of Stat3. Adv Exp Med Biol 2000;480:129–138.PubMedCrossRefGoogle Scholar
  22. Clark AJ. The mammary gland as a bioreactor: expression processing, and production of recombinant proteins. J Mammary Gland Biol Neoplasia 1998;3:337–350.PubMedCrossRefGoogle Scholar
  23. Clemmons DR, Dehoff MH, Busby WH, Bayne ML, Cascieri MA. Competition for binding to insulin-like growth factor (IGF) binding protein-2, 3, 4, and 5 by IGFs and IGF analogs. Endocrinology 1992;131:890–895.PubMedCrossRefGoogle Scholar
  24. Covarrubias L, Nishida Y, Mintz B. Early postimplantation embryo lethality due to DNA rearrangements in a transgenic mouse strain. Proc Natl Acad Sci USA 1986;83:6020–6024.PubMedCrossRefGoogle Scholar
  25. Cox DB, Owens RA, Hartmann PE. Blood and milk prolactin and the rate of milk synthesis in women. Exp Physiol 1996;81:1007–1020.PubMedGoogle Scholar
  26. Cunha GR, Young P, Horn YK, Cooke PS, Taylor JA, Lubahn DB. Elucidation of a role for stromal steroid hormone receptors in mammary gland growth and development using tissue recombinants. J Mammary Gland Biol Neoplasia 1997;2:393–402.PubMedCrossRefGoogle Scholar
  27. Daly MJ, Rioux JD, Schaffner SF, Hudson TJ, Lander ES. High-resolution haplotype structure in the human genome. Nat Genet 2001;29:229–232.PubMedCrossRefGoogle Scholar
  28. DeOme KB, Faulkin LJ Jr, Bern HA, Blair PE. Development of mammary tumors from hyperplastic alveolar nodules transplanted into gland-free mammary fat pads of female C3H mice. Cancer Res 1959; 19:515–520.Google Scholar
  29. Dulak N, Temin HM. A partially purified polypeptide fraction from rat liver cell conditioned medium with multiplication stimulating activity for embryo fibroblasts. J Cell Physiol 1972;81:153–160.CrossRefGoogle Scholar
  30. Dunbar ME, Dann P, Brown CW, Van Houton J, Dreyer B, Philbrick WP, Wysolmerski JJ. Temporally regulated overexpression of parathyroid hormone-related protein in the mammary gland reveals distinct fetal and pubertal phenotypes. J Endocrinol 2001;171:403–416.PubMedCrossRefGoogle Scholar
  31. Dymecki SM. Flp recombinase promotes site-specific DNA recombination in embryonic stem cells and transgenic mice. Proc Natl Acad Sci USA 2003;93:6191–6196.CrossRefGoogle Scholar
  32. Edwards PAW, Ward JL, Bradbury JM. Alteration of morphogenesis by the v-myc oncogene in transplants of mammary gland. Oncogene 1988;2:407–412.PubMedGoogle Scholar
  33. El Mkadem SA, Lautier C, Macari F, Molinari N, Lefèbvre P, Renard E, Gris JC, Cros G, Daurès JP, Bringer J, White MF, Grigorescu F. Role of allelic variants Gly972Arg of IRS-1 and Glyl057Asp of IRS-2 in moderate-to-severe insulin resistance of women with polycystic ovary syndrome. Diabetes 2001;50:2164–2168.PubMedCrossRefGoogle Scholar
  34. Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 2001 ;411:494–498.Google Scholar
  35. Epstein-Baak R, Lin Y, Bradshaw V, Cohn M. Inducible transformation of cells from transgenic mice expressing SV40 under lac operon control. Cell Growth Differ 1992;3:127–134.PubMedGoogle Scholar
  36. Fantin VR, Wang Q, Lienhard GE, Keller SR. Mice lacking insulin receptor substrate 4 exhibit mild defects in growth reproduction and glucose homeostasis. Am J Physiol Endocrinol Metab 2001 ;278:E 127-E 133.Google Scholar
  37. Farrelly N, Lee YJ, Oliver J, Dive C, Streuli CH. Extracellular matrix regulates apoptosis in mammary epithelium through a control on insulin signaling. J Cell Biol 1999;144:1337–1348.PubMedCrossRefGoogle Scholar
  38. Flint DJ, Tonner E, Allan GJ. Insulin-like growth factor binding proteins:IGF-dependent and -independent effects in the mammary gland. J Mammary Gland Biol Neoplasia 2000;5:65–73.PubMedCrossRefGoogle Scholar
  39. Furth PA, St Onge L, Boger H, Gruss P, Gossen M, Kistner A, Bujard H, Hennighausen L. Temporal control of gene expression in transgenic mice by a tetracycline-responsive promoter. Proc Natl Acad Sci USA 1994;91:9302–9306.PubMedCrossRefGoogle Scholar
  40. Gillespie C, Read LC, Bagley CJ, Ballard FJ. Enhanced potency of truncated insulin-like growth factor-I (des(l-3)IGF-I) relative to IGF-I in lit/lit mice. J Endocrinol 1990;127:401–405.PubMedCrossRefGoogle Scholar
  41. Gordon JW, Scangos GA, Plotkin DJ, Barbosa JA, Ruddle FH. Genetic transformation of mouse embryos by microinjection of purified DNA. Proc Natl Acad Sci USA 1980;77:7380–7384.PubMedCrossRefGoogle Scholar
  42. Gossen M, Bujard H. Studying gene function in eukaryotes by conditional gene inactivation. Annu Rev Genet 2002;36:153–173.PubMedCrossRefGoogle Scholar
  43. Grandori C, Cowley SM, James LP, Eisenman RN. The myc/max/mad network and the transcriptional control of cell behavior. Annu Rev Cell Dev Biol 2001; 16 653–699.CrossRefGoogle Scholar
  44. Gregor PD, Sawadogo M, Roeder RG. The adenovirus major late transcription factor USF is a member of the helix-loop-helix group of regulatory proteins and binds to DNA as a dimer. Genes Dev 1990;4:1730–1740.PubMedCrossRefGoogle Scholar
  45. Grisart B, Coppieters W, Farnir F, Karim L, Ford C, Berzi P, Cambisano N, Mni M, Reid S, Simon P, Spelman R, Georges M, Snell R. Positional candidate cloning of a QTL in dairy cattle: identification of a missensemutation in the bovine DGAT1 gene with major effect on milk yield and composition. Genome Res 2002;12:222–231.PubMedCrossRefGoogle Scholar
  46. Gutierrez A, Meade HM, Ditullio P, Pollock D, Harvey M, Jimenez-Flores R, Anderson GB, Murray JD, Medrano JF. Expression of a bovine kappa-CN cDNA in the mammary gland of transgenic mice utilizing a genomic milk protein gene as an expression cassette. Transgenic Res 1996;5:271–279.PubMedCrossRefGoogle Scholar
  47. Gutierrez-Adan A, Maga EA, Meade HM, Shoemaker CF, Medrano JF, Anderson GB, Murray JD. Alterations of the physical characteristics of milk from transgenic mice producing bovine k-casein. J Dairy Sci 1996;79:791–799.PubMedCrossRefGoogle Scholar
  48. Guy CT, Cardiff RD, Muller WJ. Induction of mammary tumors by expression of Polyomavirus middle T oncogene: a transgenic mouse model for metastatic disease. Mol Cell Biol 1992;12:954–961.PubMedGoogle Scholar
  49. Guy CT, Muthuswamy SK, Cardiff RD, Soriano P, Muller WJ. Activation of the c-src tyrosine kinase is required for the induction of mammary tumors in transgenic mice. Genes Dev 1996;8:23–32.CrossRefGoogle Scholar
  50. Hadsell D, Greenberg NM, Fligger JM, Baumrucker CM, Rosen JM. Targeted expression of des (1–3) human insulin-like growth factor I in transgenic mice influences mammary gland development and IGF-binding protein expression. Endocrinology 1996;137:321–330.PubMedCrossRefGoogle Scholar
  51. Hadsell DL, Bonnette SG. IGF and insulin action in the mammary gland: lessons from transgenic and knockout models. J Mammary Gland Biol Neoplasia 2000;5:19–30.PubMedCrossRefGoogle Scholar
  52. Hadsell DL, Murphy KL, Reece N, Alexeenko T, Lascerica R, Rosen JM. Cooperation between des(l-3)IGF-I and mutant p53 accelerates mammary gland carcinogenesis in bigenic mice. Oncogene 2000;19:889–898.PubMedCrossRefGoogle Scholar
  53. Hadsell DL, Alexeenko T, Klemintidis Y, Torres D, Lee AV. Inability of overexpressed des(l-3)human insulinlike growth factor I (IGF-I) to inhibit forced mammary gland involution is associated with decreased expression of IGF signaling molecules. Endocrinology 2001;142:1479–1488.PubMedCrossRefGoogle Scholar
  54. Hadsell DL, Bonnette SG, Lee AV. Genetic manipulation of the IGF-I axis to regulate mammary gland development and function. J Dairy Sci 2002;85:365–377.PubMedCrossRefGoogle Scholar
  55. Hansen LB. Consequences of selection for milk yield from a geneticist’s viewpoint. J Dairy Sci 2000;83:1145–1150.PubMedCrossRefGoogle Scholar
  56. Hennighausen L, Wall RJ, Tillmann U, Li M, Fürth PA. Conditional gene expression in secretory tissues and skin of transgenic mice using the MMTV-LTR and the tetracycline responsive system. J Cell Biochem 1995;59:463–472.PubMedCrossRefGoogle Scholar
  57. Horton RM, Hunt HD, Ho SN, Pullen JK, Pease LR. Engineering hybrid genes without the use of restriction enzymes: gene splicing by overlap extension. Gene 1989;77:61–68.PubMedCrossRefGoogle Scholar
  58. Houdebine LM. Transgenic animals as bioreactors. Transgenic Res 2000;9:305–320.PubMedCrossRefGoogle Scholar
  59. Hovey RC, Harris J, Hadsell DL, Lee AV, Ormandy CJ, Vonderhaar BK. Local insulin-like growth factor-II mediates PRL-induced mammary gland development. Mol Endocrinol 2002;17:460–471.PubMedCrossRefGoogle Scholar
  60. Hsu SY, Nakabayashi K, Nishi S, Kumagi J, Kudo M, Sherwood OD, Hsueh AJW. Activation of orphan receptors by the hormone relaxin. Science 2002;295:671–674.PubMedCrossRefGoogle Scholar
  61. Humphreys RC, Lydon J, O’Malley BW, Rosen JM. Mammary gland development is mediated by both stromal and epithelial progesterone receptors. Mol Endocrinol 1997; 11:801–811.PubMedCrossRefGoogle Scholar
  62. Hutchinson J, Jin J, Cardiff RD, Woodgett JR, Muller WJ. Activation of Akt (protein kinase B) in mammary epithelium provides a critical cell survival signal required for tumor progression. Mol Cell Biol 2001;21;2203–2212.PubMedCrossRefGoogle Scholar
  63. Iavnilovitch E, Groner B, Barash I. Overexpression and forced activation of stat5 in mammary gland of transgenic mice promotes cellular proliferation, enhances differentiation, and delays postlactational apoptosis. Mol Cancer Res 2002;1;32–47.PubMedGoogle Scholar
  64. Ivell R, Bathgate RAD. Reproductive biology of the relaxin-like growth factor (RFL/INSL3). Biology Reprod 2002;67:699–705.CrossRefGoogle Scholar
  65. Johnson GC, Esposito L, Barratt BJ, Smith AN, Heward J, Di Genova G, Ueda H, Cordell HJ, Eaves IA, Dudbridge F, Twells RC, Payne F, Hughes W, Nutland S, Stevens H, Carr P, Tuomilehto-Wolf E, Tuomilehto J, Gough SC, Clayton DG, Todd JA. Haplotype tagging for the identification of common disease genes. Nat Genet 2001;29:233–237.PubMedCrossRefGoogle Scholar
  66. Johnson MS, Thomson SC, Speakman JR. Limits to sustained energy intake. I. lactation in the laboratory mouse Mus musculus. J Exp Biol 2001;204:1925–1935.PubMedGoogle Scholar
  67. Keiper BD, Gan W, Rhoads RE. Protein synthesis initiation factor 4G. Int J Biochem Cell Biol 1999;31:37–41.PubMedCrossRefGoogle Scholar
  68. Kido Y, Burks DJ, Withers D, Bruning JC, Kahn CR, White MF, Accili D. Tissue-specific insulin resistance in mice with mutations in the insulin receptor, IRS-1 and IRS-2. J Clin Invest 2000;105:199–205.PubMedCrossRefGoogle Scholar
  69. Kleinberg DL, Ruan W, Catanese V, Newman CB, Feldman M. Non-lactogenic effects of growth hormone on growth and insulin-like growth factor-I messenger ribonucleic acid of rat mammary gland [published erratum appears in Endocrinology 1990 Oct; 127(4): 1977]. Endocrinology 1990;126:3274–3276.PubMedCrossRefGoogle Scholar
  70. Kleinberg DL, Feldman M, Ruan W. IGF-I:An essential factor in terminal end bud formation and ductal morphogenesis. J Mammary Gland Biol Neoplasia 2000;5:7–18.PubMedCrossRefGoogle Scholar
  71. Korach KS. Insights from the study of animal lacking functional estrogen receptor. Science 1994;266:1524–1527.PubMedCrossRefGoogle Scholar
  72. Kubota N, Tobe K, Terauchi Y, Kazuhiro E, Yamauchi T, Suzuki R, Tsubamoto Y, Komeda K, Nakano R, Miki H, Satoh S, Sekihara H, Sciacchitano S, Lesniak M, Aizawa S, Nagai R, Kimura S, Akanuma Y, Taylor SI, Kadowaki T. Disruption of insulin receptor substrate 2 causes type 2 diabetes because of liver insulin resistance and lack of compensatory β-cell hyperplasia. Diabetes 2000;49:1880–1889.PubMedCrossRefGoogle Scholar
  73. Kunath T, Gish G, Lickert H, Jones N, Pawson T, Rossant J. Transgenic RNA interference in ES cell-derived embryos recapitulates a genetic null phenotype. Nature Biotechnol 2003;21:559–561.CrossRefGoogle Scholar
  74. L’Huillier PJ, Soulier S, Stinnakre MG, Lepourry L, Davis SR, Mercier JC, Vilotte JL. Efficient and specific ribozyme-mediated reduction of bovine alpha-lactalbumin expression in double transgenic mice. Proc Natl Acad Sci USA 1996;93:6698–6703.PubMedCrossRefGoogle Scholar
  75. Lacy E, Costantini FD. Structure and expression of foreign globin genes in transgenic mice. Prog Clin Biol Res 1983;134:13–25.PubMedGoogle Scholar
  76. Lacy E, Roberts S, Evans EP, Burtenshaw MD, Costantini FD. A foreign beta-globin gene in transgenic mice: integration at abnormal chromosomal positions and expression in inappropriate tissues. Cell 1983;34:343–358.PubMedCrossRefGoogle Scholar
  77. Lakso M, Sauer B, Mosinger B Jr, Lee EJ, Manning RW, Yu S-H, Mulder KL, Westphal H. Targeted oncogene activation by site-specific recombination in transgenic mice. Proc Natl Acad Sci USA 1992;89:6232–6236.PubMedCrossRefGoogle Scholar
  78. Laustsen PG, Michael MD, Crute BE, Cohen SE, Ueki K, Kulkarni RN, Keller SR, Lienhard GE, Kahn CR. Lipoatrophic diabetes in Irsl-Irs3 double knockout mice. Genes Dev 2002;16:3213–3222.PubMedCrossRefGoogle Scholar
  79. Le Fur S, Le Stunff C, Bougnères P. Increased insulin resistance in obese children who have both 972 IRS-1 and 1057 IRS-2 polymorphisms. Diabetes 2002;51:S304–S307.PubMedCrossRefGoogle Scholar
  80. Le Provost F, Riedlinger G, Hee YS, Benedict J, Gonzalez FJ, Flaws J, Hennighausen L. The aryl hydrocarbon receptor (AhR) and its nuclear translocator (Arnt) are dispensable for normal mammary gland development but are required for fertility. Genesis 2002;32;231–239.PubMedCrossRefGoogle Scholar
  81. Lee KF, DeMayo FJ, Atiee SH, Rosen JM. Tissue-specific expression of the rat ß-casein gene in transgenic mice. Nucleic Acids Res 1988;16:1027–1041.PubMedCrossRefGoogle Scholar
  82. Lee AV, Zhang P, Ivanova M, Bonnette S, Oesterreich S, Rosen JM, Grimm S, Hovey RC, Vonderhaar BK, Kahn CR, Torres D, George J, Mohsin S, Allred DC, Hadsell DL. Developmental and hormonal signals dramatically alter the localization and abundance of insulin receptor substrate proteins in the mammary gland. Endocrinology 2003;144:2683–2694.PubMedCrossRefGoogle Scholar
  83. Lewis DL, Hagstrom JE, Loomis AG, Wolff JA, Herweijer H. Efficient delivery of siRNA for inhibition of gene expression in postnatal mice. Nat Genet 2002;32:107–108.PubMedCrossRefGoogle Scholar
  84. Li M, Liu X, Robinson G, Bar-Peled U, Wagner K, Young WS, Hennighausen L, Furth PA. Mammary-derived signals activate programmed cell dath during the first stage of mammary gland involution. Proc Natl Acad Sci USA 1997;94:3425–3430.PubMedCrossRefGoogle Scholar
  85. Lin TP, Guzman RC, Osborn RC, Thordarson G, Nandi S. Role of endocrine, autocrine and paracrine interactions in the development of mammary hyperplasia in wnt-1 transgenic mice. Cancer Res 1992;56:4413–4419.Google Scholar
  86. Liu SC, Wang Q, Lienhard GE, Keller SR. Insulin receptor substrate 3 is not essential for growth or glucose homeostasis. J Biol Chem 1999;274:18093–18099.PubMedCrossRefGoogle Scholar
  87. Lok S, Johnston DS, Conklin D, Lofton-Day CE, Adams RL, Jelmberg AC, Whitmore TE, Schrader S, Griswold MD, Jaspers SR. Identification of INSL6, a new member of the insulin family that is expressed in the testis of the human and rat. Biol Reprod 2000;62:1593–1599.PubMedCrossRefGoogle Scholar
  88. Lufkin T, Dierich A, LeMeur M, Mark M, Chambon P. Disruption of the Hox-1.6 homeobox gene results in defects in a region corresponding to its rostral domain of expression. Cell 1991;66:1105–1119.PubMedCrossRefGoogle Scholar
  89. Lyons WR, Li CH, Johnson RE. The hormonal control of mammary growth and lactation. Recent Prog Horm Res 1958;4:219–248.Google Scholar
  90. Madon RJ, Ensor DM, Knight CH, Flint DJ. Effects of an antiserum to rat growth hormone on lactation in the rat. J Endocrinol 1986;111:117–123.PubMedCrossRefGoogle Scholar
  91. Manche L, Green SR, Schmedt C, Mathews MB. Interactions between double-stranded RNA regulators and the proteins kinase DAI. Mol Cell Biol 1992;12:5238–5248.PubMedGoogle Scholar
  92. Marasco L, Marmet C, Shell E. Polycystic ovary syndrome: a connection to insufficient milk supply? J Hum Lact 2000;16:143–148.PubMedCrossRefGoogle Scholar
  93. Maroulakou IG, Anver M, Garrett L, Green JE. Prostate and mammary adenocarcinoma in transgenic mice carrying a rat C3(l) simian virus 40 large tumor antigen fusion gene. Proc Natl Acad Sci USA 1994;91:11236–11240.PubMedCrossRefGoogle Scholar
  94. Marquardt H, Todaro GJ, Henderson LE, Oroszlan S. Purification and primary structure of a polypeptide with multiplication-stimulating activity from rat liver cell cultures. J Biol Chem 1981;256:6859–6865.PubMedGoogle Scholar
  95. McCaffrey AP, Meuse L, Pham TT, Conklin DS, Hannon GJ, Kay MA. RNA interference in adult mice. Nature 2002;418:38–39.PubMedCrossRefGoogle Scholar
  96. McKendrick L, Pain VM, Morley SJ. Translation initiation factor 4E. Int J Biol Chem 1999;31:31–35.Google Scholar
  97. Minks MA, West DK, Envin S, Aglioni C. Structural requirements of double-stranded RNA for the activations of 2′, 5′-oligo(A) polymerase and protein kinase of interferon-treated HeLa cells. J Biol Chem 1979;254:10180–10183.PubMedGoogle Scholar
  98. Moorehead RA, Fata JE, Johnson MB, Khokha R. Inhibition of mammary epithelial apoptosis and sustained phosphorylation of Akt/PKB in MMTV-IGF-II transgenic mice. Cell Death Differ 2001;8:16–29.PubMedCrossRefGoogle Scholar
  99. Muller WJ, Sinn E, Pattengale PK, Wallace R, Leder P. Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene. Cell 1988;1:105–115.CrossRefGoogle Scholar
  100. Murata H, Hresko RC, Mueckler M. Reconstitution of PI 3-kinasae-dependent insulin signaling in a cell-free system. J Biol Chem 2003;13:21607–21614.CrossRefGoogle Scholar
  101. Nagai J, Sarkar NK. Relationship between milk yield and mammary gland development in mice. J Dairy Sci 1978;61:733–739.PubMedCrossRefGoogle Scholar
  102. Nandi S. Endocrine control of mammary gland development and function in the C3 11/HE Crgl mouse. J Natl Cancer Inst 1958;21:1039–1062.PubMedGoogle Scholar
  103. Neuenschwander S, Schwartz A, Wood TL, Roberts CTJ, Henninghausen L, LeRoith D. Involution of the lactating mammary gland is inhibited by the IGF system in a transgenic mouse model. J Clin Invest 1996;97:2225–2232.PubMedCrossRefGoogle Scholar
  104. Nguyen DA, Parlow AF, Neville MC. Hormonal regulation of tight junction closure in the mouse mammary epithelium during the transition from pregnancy to lactation. J Endocrinol 2001;170:347–356.PubMedCrossRefGoogle Scholar
  105. No D, Yao TP, Evans RM. Ecdysone-inducible gene expression in mammalian cells and transgenic mice. Proc Natl Acad Sci USA 1996;93:3346–3351.PubMedCrossRefGoogle Scholar
  106. Noble MS, Rodriguez-Zas S, Cook JB, Bleck GT, Hurley WL, Wheeler MB. Lactational performance of firstparity transgenic gilts expressing bovine alpha-lactalbumin in their milk. J Anim Sci 2002;80:1090–1096.PubMedGoogle Scholar
  107. Oftedal OT. Milk composition, milk yield and energy output at peak lactation: a comparative review. Symp Zoolog Soc (London) 1984;51:33–85.Google Scholar
  108. Ormandy CJ, Binart N, Kelly PA. Mammary gland development in prolactin receptor knockout mice. J Mammary Gland Biol Neoplasia 1997;2:355–364.PubMedCrossRefGoogle Scholar
  109. Ornitz DM, Moreadith RW, Leder P. Binary system for regulating transgene expression in mice: targeting int-2 gene expression with yeast GAL4/UAS control elements. Proc Natl Acad Sci USA 1991;88:698–702.PubMedCrossRefGoogle Scholar
  110. Paddison PJ, Caudy AA, Bernstein E, Hannon GJ. Short hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian cells. Genes Dev 2002;16:948–958.PubMedCrossRefGoogle Scholar
  111. Palmiter RD, Brinster RL, Hammer RE, Trumbauer ME, Rosenfeld MG, Birnberg NC, Evans RM. Dramatic growth of mice that develop from eggs microinjected with metallothione in growth hormone fusion genes. Nature 1982;300:611–615.PubMedCrossRefGoogle Scholar
  112. Peel CJ, Bauman DE, Gorewit RC, Sniffen CJ. Effect of exogenous growth hormone on lactational performance in high yielding dairy cows. J Nutr 1981 ; 111:1662–1671.Google Scholar
  113. Peripato AC, de Brito RA, Vaughn TT, Pletscher LS, Matioli SR, Cheverud JM. Quantitative trait loci for maternal performance for offspring survival in mice. Genetics 2002;162:1341–1353.PubMedGoogle Scholar
  114. Pittius CW, Hennighausen L, Lee E, Westphal H, Niçois E, Vitale J, Gordon K. A milk protein gene promoter directs the expression of human tissue plasminogen activator cDNA to the mammary gland in transgenic mice. Proc Natl Acad Sci USA 1988;85:5874–5878.PubMedCrossRefGoogle Scholar
  115. Plasterk RHA. RNA silencing: the genome’s immune system. Science 2002;296:1263–1265.PubMedCrossRefGoogle Scholar
  116. Pravtcheva DD, Wise TL. Metastasizing mammary carcinomas in H19 enhancers-Igf2 transgenic mice. J Exp Zool 1999;281:43–57.CrossRefGoogle Scholar
  117. Quarrie LH, Addey CV, Wilde CJ. Programmed cell death during mammary tissue involution induced by weaning, litter removal, and milk stasis. J Cell Physiol 1996;168:559–569.PubMedCrossRefGoogle Scholar
  118. Radice GL, Ferreira-Cornwell MC, Robinson SD, Rayburn H, Chodosh LA, Takeichi M, Hynes RO. Precocious mammary gland development in P-cadherin-deficient mice. J Cell Biol 1997;139:1025–1032.PubMedCrossRefGoogle Scholar
  119. Rinderknecht E, Humbel RE. Primary structure of human insulin-like growth factor II. FEBS Lett 1978a;89:283–286.PubMedCrossRefGoogle Scholar
  120. Rinderknecht E, Humbel RE. The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. J Biol Chem 1978b;253:2769–2776.PubMedGoogle Scholar
  121. Robinson GW, Hennighausen L. Inhibins and activins regulate mammary epithelial cell differentiation through mesenchymal-epithelial interactions. Development 1997;124:2701–2708.PubMedGoogle Scholar
  122. Robinson GW, Accili D, Hennighausen L. Rescue of mammary epithelium of early lethal phenotypes by embryonic mammary gland transplantation as exemplified with insulin receptor null mice. In: Ip MM, Asch BB, editors. Methods in Mammary Gland Biology and Breast Cancer Research. New York: Kluwer Academic/Plenum Publishers, 2000; pp 307–316.CrossRefGoogle Scholar
  123. Roy AL, Carruthers C, Gutjahr T, Roeder RG. Direct role for Myc in transcription initiation mediated by interactions with TFII-I. Nature 1993;365:359–361.PubMedCrossRefGoogle Scholar
  124. Roy AL, Du H, Gregor PD, Novina CD, Martinez E, Roeder RG. Cloning of an Inr- and E-box-binding protein, TFII-I, that interacts physically and functionally with USF-1. EMBO J 1997;16:7091–7104.PubMedCrossRefGoogle Scholar
  125. Ruan W, Kleinberg DL. Insulin-like growth factor I is essential for terminal end bud formation and ductal morphogenesis during mammary development. Endocrinology 1999;140:5075–5081.PubMedCrossRefGoogle Scholar
  126. Ruan W, Newman CB, Kleinberg DL. Intact and amino-terminally shortened forms of insulin-like growth factor I induce mammary gland differentiation and development. Proc Natl Acad Sci USA 1992;89:10872–10876.PubMedCrossRefGoogle Scholar
  127. Ruan W, Catanese V, Wieczorek R, Feldman M, Kleinberg DL. Estradiol enhances the stimulatory effect of insulin-like growth factor-I (IGF-I) on mammary development and growth hormone-induced IGF-I messenger ribonucleic acid. Endocrinology 1995;136:1296–1302.PubMedCrossRefGoogle Scholar
  128. Ryan AS, Wenjun Z, Acosta A. Breastfeeding continues into the new millennium. Pediatrics 2002;110:1103–1109.PubMedCrossRefGoogle Scholar
  129. Salmon WD Jr, Daughaday WH. A hormonal controlled serum factor which stimulates sulfate incorporation by cartilage in vitro. J Lab Clin Med 1957;49:825–826.PubMedGoogle Scholar
  130. Sawadogo M. Multiple forms of the human gene-specific transcription factor USF. II. DNA binding properties and transcriptional activity of the purified HeLa USF. J Biol Chem 1988;263:11994–12001.PubMedGoogle Scholar
  131. Sawadogo M, Roeder RG. Interaction of a gene-specific transcription factor with adenovirus major latepromoter upstream of the TATA box region. Cell 1985;43:165–175.PubMedCrossRefGoogle Scholar
  132. Sawai S, Shimono A, Hanaoka K, Kondoh H. Embryonic lethality resulting from disruption of both N-myc alleles in mouse zygotes. New Biol 1991;3:861–869.PubMedGoogle Scholar
  133. Schaapveld RQ, Schepens JT, Robinson GW, Attema J, Oerlemans FT, Fransen JA, Streuli M, Wieringa B, Hennighausen L, Hendriks WJ. Impaired mammary gland development and function in mice lacking LAR receptor-like tyrosine phosphatase activity. Dev Biol 1997; 188:134–146.PubMedCrossRefGoogle Scholar
  134. Schwartzberg PL, Robertson EJ, Goff SP. Targeted gene disruption of the endogenous c-abl locus by homologous recombination with DNA encoding a selectable fusion protein. Proc Natl Acad Sci USA 1989;87:3210–3214.CrossRefGoogle Scholar
  135. Schwertfeger K, Richert MM, Anderson SM. Mammary gland involution is delayed by activated akt in transgenic mice. Mol Endocrinol 2001;15:867–881.PubMedCrossRefGoogle Scholar
  136. Schwertfeger KL, McManaman JL, Palmer CA, Neville MC, Anderson SM. Expression of constitutively activated Akt in the mammary gland leads to excess lipid synthesis during pregnancy and lactation. J Lipid Res 2003;44:1100–1112.PubMedCrossRefGoogle Scholar
  137. Seagroves TN, Hadsell D, McManaman J, Palmer C, Liao D, McNulty W, Welm B, Wagner KU, Neville M, Johnson RS. HIFI alpha is a critical regulator of secretory differentiation and activation, but not vascular expansion, in the mouse mammary gland. Development 2003;130:1713–1724.PubMedCrossRefGoogle Scholar
  138. Selbert S, Bentley DJ, Melton DW, Rannie D, Lourenco P, Watson CJ, Clarke AR. Efficient BLG-Cre mediated gene deletion in the mammary gland. Transgenic Res 1998;7:387–396.PubMedCrossRefGoogle Scholar
  139. Shinagawa T, Ishii S. Generation of Ski-knockdown mice by expressing a long double-strand RNA from an RNA polymerase II promoter. Genes Dev 2003;17:1340–1345.PubMedCrossRefGoogle Scholar
  140. Shipman LJ, Docherty AH, Knight CH, Wilde CJ. Metabolic adaptations in mouse mammary gland during a normal lactation cycle and in extended lactation. Q J Exp Physiol 1987;72:303–311.PubMedGoogle Scholar
  141. Sicinski P, Donaher JL, Parker SB, Li T, Fazeli A, Gardner H, Haslma SZ, Bronson RT, Elledge SJ, Weinberg RA. Cyclin Dl provides a link between development and oncogenesis in the retina and breast. Cell 1995;82:621–630.PubMedCrossRefGoogle Scholar
  142. Simons JP, McClenaghan M, Clark AJ. Alteration of the quality of milk by expression of sheep beta-lactoglobulin in transgenic mice. Nature 1987;328:530–532.PubMedCrossRefGoogle Scholar
  143. Sinn E, Muller W, Pattengale P, Tepler I, Wallace R, Leder P. Coexpression of MMTV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: synergistic action of oncogenes in vivo. Cell 1987;49:465–475.PubMedCrossRefGoogle Scholar
  144. Sirito M, Lin Q, Maity T, Sawadogo M. Ubiquitous expression of the 43- and 44-kDa forms of transcription factor USF in mammalian cells. Nucleic Acids Res 1994;22:427–433.PubMedCrossRefGoogle Scholar
  145. Sirito M, Lin Q, Deng JM, Behringer RR, Sawadogo M. Overlapping roles and asymetrical cross-regulation of the USF proteins in mice. Proc Natl Acad Sci USA 1998;95:3758–3763.PubMedCrossRefGoogle Scholar
  146. Sohail M, Doran G, Riedemann J, Macaulay V, Southern EM. A simple and cost-effective method for producing small interfering RNAs with high efficacy. Nucleic Acids Res 2003;31 :338.CrossRefGoogle Scholar
  147. Soriano P, Gridley T, Jaenisch R. Retroviruses and insertional mutagenesis in mice: proviral integration at the Mov 34 locus leads to early embryonic death. Genes Devi987; 1:366–375.Google Scholar
  148. Soulier S, Stinnakre MG, Lepourry L, Mercier JC, Vilotte JL. Use of doxycycline-controlled gene expression to reversibly alter milk-protein composition in transgenic mice. Eur J Biochem 1999;260:533–539.PubMedCrossRefGoogle Scholar
  149. Stacey A, Bateman J, Choi T, Mascara T, Cole W, Jaenisch R. Perinatal lethal osteogenesis imperfecta in transgenic mice bearing an engineered mutant pro-alpha 1(I) collagen gene. Nature 1988;332:131–136.PubMedCrossRefGoogle Scholar
  150. Stacey A, Schnieke A, Kerr M, Scott A, McKee C, Cottingham I, Binas B, Wilde C, Colman A. Lactation is disrupted by alpha-lactalbumin deficiency and can be restored by human alpha-lactalbumin gene replacement in mice. Proc Natl Acad Sci USA 1995;92:2835–2839.PubMedCrossRefGoogle Scholar
  151. Stark GR, Kerr IM, Williams BR, Silverman RH, Schreiber RD. How cells respond to interferons. Annu Rev Biochem 1998;67:227–264.PubMedCrossRefGoogle Scholar
  152. Stewart TA, Pattengale PK, Leder P. Spontaneous mammary adenocarcinomas in transgenic MTV/myc fusion genes. Cell 1984;38:627–637.PubMedCrossRefGoogle Scholar
  153. Stinnakre MG, Vilotte JL, Soulier S, Mercier JC. Creation and phenotypic analysis of alpha-lactalbumin-deficient mice. Proc Natl Acad Sci USA 1994;91:6544–6548.PubMedCrossRefGoogle Scholar
  154. Thomas KR, Capecchi MR. Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells. Cell 1987;51:503–512.PubMedCrossRefGoogle Scholar
  155. Thompson S, Clarke AR, Pow AM, Hooper ML, Melton DW. Germ line transmission and expression of a corrected HPRT gene produced by gene targeting in embryonic stem cells. Cell 1989;56:313–321.PubMedCrossRefGoogle Scholar
  156. Tonner E, Barber MC, Allan GJ, Beattie J, Webster J, Whitelaw CB, Flint DJ. Insulin-like growth factor binding protein-5 (IGFBP-5) induces premature cell death in the mammary glands of transgenic mice. Development 2002;129:4547–4557.PubMedGoogle Scholar
  157. Tsukamoto AS, Grosshedl R, Guzman RC, Parslow T, Varmus HE. Expression of the int-1 gene in transgenic mice is associated with mammary gland hyperplasia and adenocarcinomas in male and female mice. Cell 1988;55:619–625.PubMedCrossRefGoogle Scholar
  158. Vallet VS, Henrion AA, Bucchini D, Casado M, Raymondjean M, Kahn A, Vaulont S. Glucose-dependent liver gene expression in upstream stimulatory factor 2 -/- mice. J Biol Chem 1997;272:21944–21949.PubMedCrossRefGoogle Scholar
  159. Vallet VS, Casado M, Henrion AA, Bucchini D, Raymondjean M, Kahn A, Vaulont S. Differential roles of upstream stimulatory factors 1 and 2 in the transcriptional response of liver genes to glucose. J Biol Chem 1998;273:20175–20179.PubMedCrossRefGoogle Scholar
  160. van der Putten H, Botteri F, Illmensee K. Developmental fate of a human insulin gene in a transgenic mouse. Mol Gen Genet 1984;198:128–138.PubMedCrossRefGoogle Scholar
  161. VanWyk JJ, Hall K, Van den Brande JL, Weaver RP. Further purification and characterization of sulfation factor and thymidine factor from acromegalic plasma. J Clin Endocrinol Metab 1971;32:389–403.PubMedCrossRefGoogle Scholar
  162. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG, Smith HO, Yandell M, Evans CA, Holt RA, Gocayne JD, Amanatides P, Ballew RM, Huson DH, Wormian JR, Zhang Q, Kodira CD, Zheng XH, Chen L, Skupski M, Subramanian G, Thomas PD, Zhang J, Gabor Miklos GL, Nelson C, Broder S, Clark AG, Nadeau J, McKusick VA, Zinder N, Levine AJ, Roberts RJ, Simon M, Slayman C, Hunkapiller M, Bolanos R, Delcher A, Dew I, Fasulo D, Flanigan M, Florea L, Halpern A, Hannenhalli S, Kravitz S, Levy S, Mobarry C, Reinert K, Remington K, Abu-Threideh J, Beasley E, Biddick K, Bonazzi V, Brandon R, Cargill M, Chandramouliswaran I, Charlab R, Chaturvedi K, Deng Z, Di F, V, Dunn P, Eilbeck K, Evangelista C, Gabrielian AE, Gan W, Ge W, Gong F, Gu Z, Guan P, Heiman TJ, Higgins ME, Ji RR, Ke Z, Ketchum KA, Lai Z, Lei Y, Li Z, Li J, Liang Y, Lin X, Lu F, Merkulov GV, Milshina N, Moore HM, Naik AK, Narayan VA, Neelam B, Nusskem D, Rusch DB, Salzberg S, Shao W, Shue B, Sun J, Wang Z, Wang A, Wang X, Wang J, Wei M, Wides R, Xiao C, Yan C, Yao A, Ye J, Zhan M, Zhang W, Zhang H, Zhao Q, Zheng L, Zhong F, Zhong W, Zhu S, Zhao S, Gilbert D, Baumhueter S, Spier G, Carter C, Cravchik A, Woodage T, Ali F, An H, Awe A, Baldwin D, Baden H, Barnstead M, Barrow I, Beeson K, Busam D, Carver A, Center A, Cheng ML, Curry L, Danaher S, Davenport L, Desilets R, Dietz S, Dodson K, Doup L, Ferriera S, Garg N, Gluecksmann A, Hart B, Haynes J, Haynes C, Heiner C, Hladun S, Hostin D, Houck J, Howland T, Ibegwam C, Johnson J, Kalush F, Kline L, Koduru S, Love A, Mann F, May D, McCawley S, Mcintosh T, McMullen I, Moy M, Moy L, Murphy B, Nelson K, Pfannkoch C, Pratts E, Puri V, Qureshi H, Reardon M, Rodriguez R, Rogers YH, Romblad D, Ruhfel B, Scott R, Sitter C, Smallwood M, Stewart E, Strong R, Suh E, Thomas R, Tint NN, Tse S, Vech C, Wang G, Wetter J, Williams S, Williams M, Windsor S, Winn-Deen E, Wolfe K, Zaveri J, Zaveri K, Abril JF, Guigo R, Campbell MJ, Sjolander KV, Karlak B, Kejariwal A, Mi H, Lazareva B, Hatton T, Narechania A, Diemer K, Muruganujan A, Guo N, Sato S, Bafna V, Istrail S, Lippert R, Schwartz R, Walenz B, Yooseph S, Allen D, Basu A, Baxendale J, Blick L, Caminha M, Carnes-Stine J, Caulk P, Chiang YH, Coyne M, Dahlke C, Mays A, Dombroski M, Donnelly M, Ely D, Esparham S, Fosler C, Gire H, Glanowski S, Glasser K, Glodek A, Gorokhov M, Graham K, Gropman B, Harris M, Heil J, Henderson S, Hoover J, Jennings D, Jordan C, Jordan J, Kasha J, Kagan L, Kraft C, Levitsky A, Lewis M, Liu X, Lopez J, Ma D, Majoros W, McDaniel J, Murphy S, Newman M, Nguyen T, Nguyen N, Nodell M. The sequence of the human genome. Science 2001;291:1304–1351.PubMedCrossRefGoogle Scholar
  163. Vilotte JL. Lowering the milk lactose in vivo: potential interests, strategies, and physiological consequences. Reprod Nutr Dev 2002;42:127–132.PubMedCrossRefGoogle Scholar
  164. Wagner KU, Wall RJ, St Onge L, Gruss P, Wynshaw-Boris A, Garrett L, Li M, Furth PA, Hennighausen L. Cre-mediated gene deletion in the mammary gland. Nucleic Acids Res 1997;25:4323–4330.PubMedCrossRefGoogle Scholar
  165. Wagner KU, McAllister K, Ward T, Davis B, Wiseman R, Hennighausen L. Spatial and temporal expression of the cre gene under the control of the MMTV-LTR in different lines of transgenic mice. Transgenic Res 2001;10:545–553.PubMedCrossRefGoogle Scholar
  166. Walton KD, Wagner KU, Rucker EB III, Shillingford JM, Miyoshi K, Hennighausen L. Conditional deletion of the bcl-x gene from mouse mammary epithelium results in accelerated apoptosis during involution but does not compromise cell function during lactation. Mech Dev 2001;109:281–293.PubMedCrossRefGoogle Scholar
  167. Wang Y, DeMayo FJ, Tsai SY, O’Malley BW. Ligand-inducible and liver-specific target gene expression in transgenic mice. Nat Biotechnol 1997;15:239–243.PubMedCrossRefGoogle Scholar
  168. Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, Agarwal P, Agarwala R, Ainscough R, Alexandersson M, An P, Antonarakis SE, Attwood J, Baertsch R, Bailey J, Barlow K, Beck S, Berry E, Birren B, Bloom T, Bork P, Botcherby M, Bray N, Brent MR, Brown DG, Brown SD, Bult C, Burton J, Butler J, Campbell RD, Carninci P, Cawley S, Chiaromonte F, Chinwalla AT, Church DM, Clamp M, Clee C, Collins FS, Cook LL, Copley RR, Coulson A, Couronne O, Cuff J, Curwen V, Cutts T, Daly M, David R, Davies J, Delehaunty KD, Deri J, Dermitzakis ET, Dewey C, Dickens NJ, Diekhans M, Dodge S, Dubchak I, Dunn DM, Eddy SR, Elnitski L, Ernes RD, Eswara P, Eyras E, Felsenfeld A, Fewell GA, Flicek P, Foley K, Frankel WN, Fulton LA, Fulton RS, Furey TS, Gage D, Gibbs RA, Glusman G, Gnerre S, Goldman N, Goodstadt L, Grafham D, Graves TA, Green ED, Gregory S, Guigo R, Guyer M, Hardison RC, Haussier D, Hayashizaki Y, Hillier LW, Hinrichs A, Hlavina W, Holzer T, Hsu F, Hua A, Hubbard T, Hunt A, Jackson I, Jaffe DB, Johnson LS, Jones M, Jones TA, Joy A, Kamal M, Karlsson EK, Karolchik D, Kasprzyk A, Kawai J, Keibler E, Kells C, Kent WJ, Kirby A, Kolbe DL, Korf I, Kucherlapati RS, Kulbokas EJ, Kulp D, Landers T, Leger JP, Leonard S, Letunic I, Levine R, Li J, Li M, Lloyd C, Lucas S, Ma B, Maglott DR, Mardis ER, Matthews L, Mauceli E, Mayer JH, McCarthy M, McCombie WR, McLaren S, McLay K, McPherson JD, Meldrim J, Meredith B, Mesirov JP, Miller W, Miner TL, Mongin E, Montgomery KT, Morgan M, Mort R, Mullikin JC, Muzny DM, Nash WE, Nelson JO, Nhan MN, Nicol R, Ning Z, Nusbaum C, O’Connor MJ, Okazaki Y, Oliver K, Overton-Larty E, Pachter L, Parra G, Pepin KH, Peterson J, Pevzner P, Plumb R, Pohl CS, Poliakov A, Ponce TC, Ponting CP, Potter S, Quail M, Reymond A, Roe BA, Roskin KM, Rubin EM, Rust AG, Santos R, Sapojnikov V, Schultz B, Schultz J, Schwartz MS, Schwartz S, Scott C, Seaman S, Searle S, Sharpe T, Sheridan A, Shownkeen R, Sims S, Singer JB, Slater G, Smit A, Smith DR, Spencer B, Stabenau A, Stange-Thomann N, Sugnet C, Suyama M, Tester G, Thompson J, Torrents D, Trevaskis E, Tromp J, Ucla C, Ureta-Vidal A, Vinson JP, Von Niederhausern AC, Wade CM, Wall M, Weber RJ, Weiss RB, Wendl MC, West AP, Wetterstrand K, Wheeler R, Whelan S, Wierzbowski J, Willey D, Williams S, Wilson RK, Winter E, Worley KC, Wyman D, Yang S, Yang SP, Zdobnov EM, Zody MC, Lander ES. Initial sequencing and comparative analysis of the mouse genome. Nature 2002;420:520–562.PubMedCrossRefGoogle Scholar
  169. Wiltshire T, Pletcher MT, Batalov S, Barnes SW, Tarantino LM, Cooke MP, Wu H, Smylie K, Santrosyan A, Copeland NG, Jenkins NA, Kalush F, Mural RJ, Glynne RJ, Kay SA, Adams MD, Fletcher CF. Genome-wide single-nucleotide polymorphism analysis defines haplotype patterns in mouse. Proc Natl Acad Sci USA 2003;100:3380–3385.PubMedCrossRefGoogle Scholar
  170. Wintermantel TM, Mayer AK, Schutz G, Greiner EF. Targeting mammary epithelial cells using a bacterial artificial chromosome. Genesis 2002;33:125–130.PubMedCrossRefGoogle Scholar
  171. Withers DJ, Gutierrez JS, Towery H, Burks DJ, Ren JM, Previs S, Zhang Y, Bernal D, Pons S, Shulman GI, Bonner-Wier S, White MF. Disruption of IRS-2 causes type 2 diabetes in mice. Nature 1998;391:900–904.PubMedCrossRefGoogle Scholar
  172. Withers DJ, Burks DJ, Towery HH, Altamuro SL, Flint CL, White MF. Irs-2 coordinates Igf-1 receptor-mediated β-cell development and perhipheral insulin signalling. Nat Genet 1999;23:32–40.PubMedGoogle Scholar
  173. Wolf E, Jehle PM, Weber MM, Sauerwein H, Daxenberger A, Breier BH, Besenfelder U, Frenyo L, Brem G. Human insulin-like growth factor I (IGF-I) produced in the mammary glands of transgenic rabbits: yield, receptor binding, mitogenic activity, and effects on IGF-binding proteins. Endocrinology 1997;138:307–313.PubMedCrossRefGoogle Scholar
  174. Wood TL, Richert MM, Stull MA, Allar MA. The insulin-like growth factors (IGFs) and IGF binding proteins in postnatal development of murine mammary glands. J Mammary Gland Biol Neoplasia 2000;5:31–42.PubMedCrossRefGoogle Scholar
  175. Working Group on Breastfeeding. Breastfeeding and the use of human milk (RE9729). Pediatrics 1997;100:1035–1039.CrossRefGoogle Scholar
  176. Wysolmerski JJ, McCaughern-Carucci JF, Daifotis AG, Broadus AE, Philbrick WM. Overexpression of parathyroid hormone-related protein or parathyroid hormone in transgenic mice impairs branching morphogenesis during mammary gland development. Development 1995;121:3539–3547.PubMedGoogle Scholar
  177. Xia H, Mao Q, Paulson HL, Davidson BL. siRNA-mediated gene silencing in vitro and in vivo. Nat Biotechnol 2002;20:1006–1010.PubMedCrossRefGoogle Scholar
  178. Yu SH, Deen KC, Lee E, Hennighausen L, Sweet RW, Rosenberg M, Westphal H. Functional human CD4 protein produced in milk of transgenic mice. Mol Biol Med 1989;6:255–261.PubMedGoogle Scholar
  179. Yu J, DeRuiter SL, Turner DL. RNA interference by expression of short-interfering RNAs and hairpin RNAs in mammalian cells. Proc Natl Acad Sci USA 2002;99:6047–6052.PubMedCrossRefGoogle Scholar
  180. Zamore PD. Ancient pathways programmed by small RNAs. Science 2002;296:1265–1269.PubMedCrossRefGoogle Scholar
  181. Zijlstra M, Li E, Sajjadi F, Subramani S, Jaenisch R. Germ-line transmission of a disrupted beta 2-microglobulin gene produced by homologous recombination in embryonic stem cells. Nature 1989;342:435–438.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2004

Authors and Affiliations

  • Darryl L. Hadsell
    • 1
  1. 1.The USDA/ARS Children’s Nutrition Research Center, Department of PediatricsBaylor College of MedicineHoustonUSA

Personalised recommendations