Skip to main content
SpringerLink
Log in

Size Matters: Use of YACs, BACs and PACs in Transgenic Animals

  • Published:
Transgenic Research Aims and scope Submit manuscript

Abstract

In 1993, several groups, working independently, reported the successful generation of transgenic mice with yeast artificial chromosomes (YACs) using standard techniques. The transfer of these large fragments of cloned genomic DNA correlated with optimal expression levels of the transgenes, irrespective of their location in the host genome. Thereafter, other groups confirmed the advantages of YAC transgenesis and position-independent and copy number-dependent transgene expression were demonstrated in most cases. The transfer of YACs to the germ line of mice has become popular in many transgenic facilities to guarantee faithful expression of transgenes. This technique was rapidly exported to livestock and soon transgenic rabbits, pigs and other mammals were produced with YACs. Transgenic animals were also produced with bacterial or P1-derived artificial chromosomes (BACs/PACs) with similar success. The use of YACs, BACs and PACs in transgenesis has allowed the discovery of new genes by complementation of mutations, the identification of key regulatory sequences within genomic loci that are crucial for the proper expression of genes and the design of improved animal models of human genetic diseases. Transgenesis with artificial chromosomes has proven useful in a variety of biological, medical and biotechnological applications and is considered a major breakthrough in the generation of transgenic animals. In this report, we will review the recent history of YAC/BAC/PAC-transgenic animals indicating their benefits and the potential problems associated with them. In this new era of genomics, the generation and analysis of transgenic animals carrying artificial chromosome-type transgenes will be fundamental to functionally identify and understand the role of new genes, included within large pieces of genomes, by direct complementation of mutations or by observation of their phenotypic consequences.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Acquati F, Hammer R, Ercoli B, Mooser V, Tao R, Ronicke V et al. (1999) Transgenic mice expressing a human apolipoprotein[a] allele. J Lipid Res 40: 994–1006.

    Google Scholar 

  • Ainscough JF, Koide T, Tada M, Barton S and Surani MA (1997) Imprinting of Igf2 and H19 from a 130 kb YAC transgene. Development 124: 3621–3632.

    Google Scholar 

  • Alami R, Greally JM, Tanimoto K, Hwang S, Feng YQ, Engel JD et al. (2000) Beta-globin YAC transgenes exhibit uniform expression levels but position effect variegation in mice. Hum Mol Genet 9: 631–636.

    Google Scholar 

  • Allan CM, Walker D and Taylor JM (1995) Evolutionary duplication of a hepatic control region in the human apolipoprotein E gene locus. Identification of a second region that confers high level and liver-specific expression of the human apolipoprotein E gene in transgenic mice. J Biol Chem 270: 26278–26281.

    Google Scholar 

  • Antoch MP, Song EJ, Chang AM, Vitaterna MH, Zhao Y, Wilsbacher LD et al. (1997) Functional identification of the mouse circadian Clock gene by transgenic BAC rescue. Cell 89: 655–667.

    Google Scholar 

  • Asselbergs FA, Grossenbacher R, Ortmann R, Hengerer B, McMaster GK, Sutter E et al. (1998) Position-independent expression of a human nerve growth factor-luciferase reporter gene cloned on a yeast artificial chromosome vector. Nucleic Acids Res 26: 1826–1833.

    Google Scholar 

  • Bartolomei MS, Webber AL, Brunkow ME and Tilghman SM (1993) Epigenetic mechanisms underlying the imprinting of the mouse H19 gene. Genes Dev 7: 1663–1673.

    Google Scholar 

  • Bauchwitz R and Costantini F (1998) YAC transgenesis: a study of conditions to protect YAC DNA from breakage and a protocol for transfection. Biochim Biophys Acta 1401: 21–37.

    Google Scholar 

  • Beermann F, Ruppert S, Hummler E, Bosc FX, Muller G, Ruther U et al. (1990) Rescue of the albino phenotype by introduction of a functional tyrosinase gene into mice. EMBO J 9: 2819–2826.

    Google Scholar 

  • Bender MA, Michael Bulger, Jennie Close, and Mark Groudine (2000) β-globin gene switching and DNase I sensitivity of the endogenous β-globin locus in mice do not require the locus control region. Mol Cell 5: 387–393.

    Google Scholar 

  • Birren B, Mancino V and Shizuya H (1999) Bacterial artificial chromosomes. In: Green ED, Birren B, Klapholz S, Myers RM and Hieter P (eds) Genome Analysis. A Laboratory Manual (vol III, Cloning Systems) (pp. 241–295) Cold Spring Harbor Laboratory Press, USA.

    Google Scholar 

  • Boren J, Lee I, Callow MJ, Rubin EM and Innerarity TL (1996) A simple and efficient method for making site-directed mutants, deletions, and fusions of large DNA such as P1 and BAC clones. Genome Res 6: 1123–1130.

    Google Scholar 

  • Brem G, Besenfelder U, Aigner B, Muller M, Liebl I, Schutz G et al. (1996) YAC transgenesis in farm animals: rescue of albinism in rabbits. Mol Reprod Dev 44: 56–62.

    Google Scholar 

  • Brinster RL, Chen HY, Trumbauer ME, Yagle MK and Palmiter RD (1985). Factors affecting the efficiency of introducing foreign DNA into mice by microinjecting eggs. Proc Natl Acad Sci USA 82: 4438–4442.

    Google Scholar 

  • Brinster RL, Allen JM, Behringer RR, Gelinas RE and Palmiter RD (1988) Introns increase transcriptional efficiency in transgenic mice. Proc Natl Acad Sci USA 85: 836–840.

    Google Scholar 

  • Brune W, Menard C, Hobom U, Odenbreit S, Messerle M and Koszinowski UH (1999) Rapid identification of essential and nonessential herpesvirus genes by direct transposon mutagenesis. Nat Biotechnol 17: 360–364.

    Google Scholar 

  • Buchholz F, Angrand PO and Stewart AF (1996) A simple assay to determine the functionality of Cre or FLP recombination targets in genomic manipulation constructs. Nucleic Acids Res 24: 3118–3119.

    Google Scholar 

  • Bungert J, Dave U, Lim KC, Lieuw KH, Shavit JA, Liu Q et al. (1995) Synergistic regulation of human beta-globin gene switching by locus control region elements HS3 and HS4. Genes Dev 9: 3083–3096.

    Google Scholar 

  • Bungert J, Tanimoto K, Patel S, Liu Q, Fear M and Engel JD (1999) Hypersensitive site 2 specifies a unique function within the human beta-globin locus control region to stimulate globin gene transcription. Mol Cell Biol 19: 3062–3072.

    Google Scholar 

  • Burke DT, Carle GF and Olson MV (1987) Cloning of large segments of exogenous DNA into yeast by means of artificial chromosome vectors. Science 236: 806–812.

    Google Scholar 

  • Butzler C, Zou X, Popov AV and Bruggemann M (1997) Rapid induction of B-cell lymphomas in mice carrying a human IgH/cmycYAC. Oncogene 14: 1383–1388.

    Google Scholar 

  • Calzolari R, McMorrow T, Yannoutsos N, Langeveld A and Grosveld F (1999) Deletion of a region that is a candidate for the difference between the deletion forms of hereditary persistence of fetal hemoglobin and deltabeta-thalassemia affects beta-but not gamma-globin gene expression. EMBO J 18: 949–958.

    Google Scholar 

  • Camper SA and Saunders TL (2000) Transgenic rescue of mutant phenotypes using large DNA fragments. In: Accili D (ed). Genetic Manipulation of Receptor Expression and Function. (pp. 1–22) Wiley, New York.

    Google Scholar 

  • Cemal CK, Huxley C and Chamberlain S (1999) Insertion of expanded CAG trinucleotide repeat motifs into a yeast artificial chromosome containing the human Machado-Joseph disease gene. Gene 236: 53–61.

    Google Scholar 

  • Chang JC, Lu R, Lin C, Xu SM, Kan YW, Porcu S et al. (1998) Transgenic knockout mice exclusively expressing human hemoglobin S after transfer of a 240-kb betas-globin yeast artificial chromosome: A mouse model of sickle cell anemia. Proc Natl Acad Sci USA 95: 14886–14890.

    Google Scholar 

  • Chiu CH, Amemiya CT, Carr JL, Bhargava J, Hwang JK, Shashikant CS et al. (2000) A recombinogenic targeting method to modify large-inserts for cis-regulatory analysis in transgenic mice: construction and expression of a 100-kb, zebrafish hoxa-11b-lacZ reporter gene. Dev Genes Evol 210: 105–109.

    Google Scholar 

  • Choi T, Huang M, Gorman C and Jaenisch R (1991) A generic intron increases gene expression in transgenic mice. Mol Cell Biol 6: 3070–3074

    Google Scholar 

  • Choi TK, Hollenbach PW, Pearson BE, Ueda RM, Weddell GN, Kurahara CG et al. (1993) Transgenic mice containing a human heavy chain immunoglobulin gene fragment cloned in a yeast artificial chromosome. Nat Genet 4: 117–123.

    Google Scholar 

  • Chrast R, Scott HS and Antonarakis SE (1999) Linearization and purification of BAC DNA for the development of transgenic mice. Transgenic Res 8: 147–150.

    Google Scholar 

  • Chung JH, Whiteley M and Felsenfeld G (1993) A 5′ element of the chicken beta-globin domain serves as an insulator in human erythroid cells and protects against position effect in Drosophila. Cell 74: 505–514.

    Google Scholar 

  • Clark AJ (1997) Transgene rescue. In: Houdebine LM (ed.) Transgenic Animals, Generation and Use. (pp. 267–272) Harwood Academic Publishers, The Netherlands.

    Google Scholar 

  • Cocchia M, Kouprina N, Kim SJ, Larionov V, Schlessinger D and Nagaraja R (2000) Recovery and potential utility of YACs as circular YACs/BACs. Nucleic Acids Res 28: E81.

    Google Scholar 

  • Compton ST, Henning KA, Chen M, Mansoura MK and Ashlock MA (1999) An improved method for routine preparation of intact artificial chromosome DNA (340–1000 kb) for transfection into human cells. Nucleic Acids Res 27: 1762–1765.

    Google Scholar 

  • Davies NP, Rosewell IR, Richardson JC, Cook GP, Neuberger MS, Brownstein BH et al. (1993) Creation of mice expressing human antibody light chains by introduction of a yeast artificial chromosome containing the core region of the human immunoglobulin kappa locus. Biotechnology (NY) 11: 911–914.

    Google Scholar 

  • Dewar K, Birren BW and Abderrahim H (1997) Bacterial artificial chromosomes and animal transgenesis. In: Houdebine LM (ed.) Transgenic Animals, Generation and Use. (pp. 283–287) Harwood Academic Publishers, The Netherlands.

    Google Scholar 

  • Dillon N and Grosveld F (1994) Chromatin domains as potential units of eukaryotic gene function. Curr Opin Genet Dev 4: 260–264.

    Google Scholar 

  • de Winther MP, van Dijk KW, van Vlijmen BJ, Gijbels MJ, Heus JJ, Wijers ER et al. (1999) Macrophage specific overexpression of the human macrophage scavenger receptor in transgenic mice, using a 180-kb yeast artificial chromosome, leads to enhanced foam cell formation of isolated peritoneal macrophages. Atherosclerosis 147: 339–347.

    Google Scholar 

  • Duff K, McGuigan A, Huxley C, Schulz F and Hardy J (1994) Insertion of a pathogenic mutation into a yeast artificial chromosome containing the human amyloid precursor protein gene. Gene Ther 1: 70–75.

    Google Scholar 

  • Duff K, Knight H, Refolo LM, Sanders S, Yu X, Picciano M et al. (2000) Characterization of pathology in transgenic mice overexpressing human genomic and cDNA tau transgenes. Neurobiol Dis 7: 87–98.

    Google Scholar 

  • Ebrahimi FA, Edmondson J, Rothstein R and Chess A (2000) YAC transgene-mediated olfactory receptor gene choice. Dev Dyn 217: 225–231.

    Google Scholar 

  • Elgin SCR (1990) Chromatin structure and gene activity. Curr Opin Cell Biol 2: 437–445.

    Google Scholar 

  • Elson DA and Bartolomei MS (1997) A 5′ differentially methylated sequence and the 3′-flanking region are necessary for H19 transgene imprinting. Mol Cell Biol 17: 309–317.

    Google Scholar 

  • Epner E, Reik A, Cimbora D, Telling A, Bender MA, Fiering S et al. (1998) The beta-globin LCR is not necessary for an open chromatin structure or developmentally regulated transcription of the native mouse beta-globin locus. Mol Cell 2: 447–455.

    Google Scholar 

  • Fan J, Wang J, Bensadoun A, Lauer SJ, Dang Q, Mahley RW et al. (1994) Overexpression of hepatic lipase in transgenic rabbits leads to a marked reduction of plasma high density lipoproteins and intermediate density lipoproteins. Proc Natl Acad Sci USA 91: 8724–8728.

    Google Scholar 

  • Fiering S, Epner E, Robinson K, Zhuang Y, Telling A, Hu M et al. (1995) Targeted deletion of 5′HS2 of the murine beta-globin LCR reveals that it is not essential for proper regulation of the beta-globin locus. Genes Dev 9: 2203–2213.

    Google Scholar 

  • Fishwild DM, O'Donnell SL, Bengoechea T, Hudson DV, Harding F, Bernhard SL et al. (1996) High-avidity human IgG kappa monoclonal antibodies from a novel strain of minilocus transgenic mice. Nat Biotechnol 14: 845–851.

    Google Scholar 

  • Forget BG (1993) YAC transgenes: bigger is probably better. Proc Natl Acad Sci USA 90: 7909–7911.

    Google Scholar 

  • Frazer KA, Narla G, Zhang JL and Rubin EM (1995) The apolipoprotein(a) gene is regulated by sex hormones and acute-phase inducers in YAC transgenic mice. Nat Genet 9: 424–431.

    Google Scholar 

  • Frazer KA, Ueda Y, Zhu Y, Gifford VR, Garofalo MR, Mohandas N et al. (1997) Computational and biological analysis of 680 kb of DNA sequence from the human 5q31 cytokine gene cluster region. Genome Res 7: 495–512.

    Google Scholar 

  • Fujiwara Y, Miwa M, Takahashi R, Hirabayashi M, Suzuki T and Ueda M (1997) Position-independent and high-level expression of human alpha-lactalbumin in the milk of transgenic rats carrying a 210-kb YAC DNA. Mol Reprod Dev 47: 157–163.

    Google Scholar 

  • Fujiwara Y, Miwa M, Takahashi R, Kodaira K, Hirabayashi M, Suzuki T et al. (1999a) High-level expressing YAC vector for transgenic animal bioreactors. Mol Reprod Dev 52: 414–420.

    Google Scholar 

  • Fujiwara Y, Takahashi RI, Miwa M, Kameda M, Kodaira K, Hirabayashi M et al. (1999b) Analysis of control elements for position-independent expression of human alpha-lactalbumin YAC. Mol Reprod Dev 54: 17–23.

    Google Scholar 

  • Gaensler KM, Kitamura M and Kan YW (1993) Germ-line transmission and developmental regulation of a 150-kb yeast artificial chromosome containing the human beta-globin locus in transgenic mice. Proc Natl Acad Sci USA 90: 11381–11385.

    Google Scholar 

  • Ganss R, Montoliu L, Monaghan AP and Schutz G (1994) A cellspecific enhancer far upstream of the mouse tyrosinase gene confers high level and copy number-related expression in transgenic mice. Embo J 13: 3083–3093.

    Google Scholar 

  • Giraldo P, Gimenez E and Montoliu L (1999) The use of yeast artificial chromosomes in transgenic animals: expression studies of the tyrosinase gene in transgenic mice. Genet Anal 15: 175–178.

    Google Scholar 

  • Gnirke A, Huxley C, Peterson K and Olson MV (1993) Microinjection of intact 200-to 500-kb fragments of YAC DNA into mammalian cells. Genomics 15: 659–667.

    Google Scholar 

  • Goodart SA, Huynh C, Chen W, Cooper AD and Levy-Wilson B (1999) Expression of the human cholesterol 7alpha-hydroxylase gene in transgenic mice. Biochem Biophys Res Commun 266: 454–459.

    Google Scholar 

  • Green ED, Hieter P and Spencer FA (1999) Yeast artificial chromosomes. In: Green ED, Birren B, Klapholz S, Myers RM and Hieter P (eds) Genome Analysis. A Laboratory Manual (vol III, Cloning Systems) (pp. 297–565) Cold Spring Harbor Laboratory Press, USA.

    Google Scholar 

  • Green LL, Hardy MC, Maynard-Currie CE, Tsuda H, Louie DM, Mendez MJ et al. (1994) Antigen-specific human monoclonal antibodies from mice engineered with human Ig heavy and light chain YACs. Nat Genet 7: 13–21.

    Google Scholar 

  • Grosveld F, van Assenfeldt GB, Greaves D and Kollias G (1987) Position-independent, high-level expression of the human betaglobin gene in transgenic mice. Cell 51: 975–985.

    Google Scholar 

  • Gutierrez-Adan A and Pintado B (2000) Effect of flanking matrix regions on the expression of microinjected transgenes during preimplantation development of mouse embryos. Transgenic Res 9: 81–89.

    Google Scholar 

  • Hamer L, Johnston M and Green ED (1995) Isolation of yeast artificial chromosomes free of endogenous yeast chromosomes: construction of alternate hosts with defined karyotypic alterations. Proc Natl Acad Sci USA 92: 11706–11710.

    Google Scholar 

  • Heard E, Kress C, Mongelard F, Courtier B, Rougeulle C, Ashworth A et al. (1996) Transgenic mice carrying an Xist-containing YAC. Hum Mol Genet 5: 441–450.

    Google Scholar 

  • Heard E, Mongelard F, Arnaud D, Chureau C, Vourc'h C and Avner P (1999a). Human XIST yeast artificial chromosome transgenes show partial X inactivation center function in mouse embryonic stem cells. Proc Natl Acad Sci USA 96: 6841–6846.

    Google Scholar 

  • Heard E, Mongelard F, Arnaud D and Avner P (1999b) Xist yeast artificial chromosome transgenes function as X-inactivation centers only in multicopy arrays and not as single copies. Mol Cell Biol 19: 3156–3166.

    Google Scholar 

  • Heintz N (2000) Analysis of mammalian central nervous system gene expression and function using bacterial artificial chromosome-mediated transgenesis. Hum Mol Genet 9: 937–943.

    Google Scholar 

  • Hiemisch H, Schutz G and Kaestner KH (1997) Transcriptional regulation in endoderm development: characterization of an enhancer controlling Hnf3g expression by transgenesis and targeted mutagenesis. EMBO J 16: 3995–4006.

    Google Scholar 

  • Hiemisch H, Umland T, Montoliu L and Schutz G (1998) The generation of transgenic mice with yeast artifiial chromosomes. In: Cid-Arregui A and García-Carrancá A (eds) Microinjection and Transgenesis, Strategies and Protocols (pp. 297–308) Springer-Verlag, Berlin Heidelberg.

    Google Scholar 

  • Hodgson JG, Smith DJ, McCutcheon K, Koide HB, Nishiyama K, Dinulos MB et al. (1996) Human huntingtin derived from YAC transgenes compensates for loss of murine huntingtin by rescue of the embryonic lethal phenotype. Hum Mol Genet 5: 1875–1885.

    Google Scholar 

  • Hodgson JG, Agopyan N, Gutekunst CA, Leavitt BR, LePiane F, Singaraja R et al. (1999) A YAC mouse model for Huntington's disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration. Neuron 23: 181–192.

    Google Scholar 

  • Huxley C, Passage E, Manson A, Putzu G, Figarella-Branger D, Pellissier JF et al. (1996) Construction of a mouse model of Charcot-Marie-Tooth disease type 1A by pronuclear injection of human YAC DNA. Hum Mol Genet 5: 563–569.

    Google Scholar 

  • Huxley C (1998) Exploring gene function: use of yeast artificial chromosome transgenesis. Methods 2: 199–210.

    Google Scholar 

  • Ioannou PA, Amemiya CT, Garnes J, Kroisel PM, Shizuya H, Chen C et al. (1994) A new bacteriophage P1-derived vector for the propagation of large human DNA fragments. Nat Genet 6: 84–89.

    Google Scholar 

  • Jakobovits A, Moore AL, Green LL, Vergara GJ, Maynard-Currie CE, Austin HA et al. (1993) Germ-line transmission and expression of a human-derived yeast artificial chromosome. Nature 362: 255–258.

    Google Scholar 

  • Jakobovits A (1994) YAC vectors. Humanizing the mouse genome. Curr Biol 4: 761–763.

    Google Scholar 

  • Jakobovits A, Lamb BT and Peterson KR (1999) Technical considerations for the generation of YAC transgenic animals. In: Tuan RS and Lo CW (eds), Methods in Molecular Biology, vol. 136: Developmental Biology Protocols, Vol. II, (pp. 435–453) Humana Press, Totowa, N.J.

    Google Scholar 

  • Jessen JR, Meng A, McFarlane RJ, Paw BH, Zon LI, Smith GR et al. (1998) Modification of bacterial artificial chromosomes through chi-stimulated homologous recombination and its application in zebrafish transgenesis. Proc Natl Acad Sci USA 95: 5121–5126.

    Google Scholar 

  • Jessen JR, Willett CE and Lin S (1999) Artificial chromosome transgenesis reveals long-distance negative regulation of rag1 in zebrafish. Nat Genet 23: 15–16.

    Google Scholar 

  • Kaufman RM, Pham CT and Ley TJ (1999) Transgenic analysis of a 100-kb human beta-globin cluster-containing DNA fragment propagated as a bacterial artificial chromosome. Blood 94: 3178–3184.

    Google Scholar 

  • Kluppel M, Beermann F, Ruppert S, Schmid E, Hummler E and Schutz G (1991) The mouse tyrosinase promoter is sufficient for expression in melanocytes and in the pigmented epithelium of the retina. Proc Natl Acad Sci USA 88: 3777–3781.

    Google Scholar 

  • Kuhn RM and Ludwig RA (1994) Complete sequence of the yeast artificial chromosome cloning vector pYAC4. Gene 141: 125–127.

    Google Scholar 

  • La Spada AR, Peterson KR, Meadows SA, McClain ME, Jeng, G, Chmelar RS et al. (1998) Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability. Hum Mol Genet 7: 959–967.

    Google Scholar 

  • Laemmli UK, Käs E, Poljak L and Adachi Y (1992) Scaffoldassociated regions: cis-acting determinants of chromatin structural loops and functional domains.Curr Opin Genet Dev 2: 275–285.

    Google Scholar 

  • Lakshmanan G, Lieuw KH, Grosveld F and Engel JD (1998) Partial rescue of GATA-3 by yeast artificial chromosome transgenes. Dev Biol 204: 451–463.

    Google Scholar 

  • Lakshmanan G, Lieuw KH, Lim KC, Gu Y, Grosveld F, Engel JD et al. (1999) Localization of distant urogenital system-, central nervous system-, and endocardium-specific transcriptional regulatory elements in the GATA-3 locus. Mol Cell Biol 19: 1558–1568.

    Google Scholar 

  • Lamb BT, Sisodia SS, Lawler AM, Slunt HH, Kitt CA, Kearns WG et al. (1993) Introduction and expression of the 400 kilobase amyloid precursor protein gene in transgenic mice. Nat Genet 5: 22–30.

    Google Scholar 

  • Lamb BT and Gearhart JD (1995) YAC transgenics and the study of genetics and human disease. Curr Opin Genet Dev 5: 342–348.

    Google Scholar 

  • Lamb BT, Call LM, Slunt HH, Bardel KA, Lawler AM, Eckman CB et al. (1997) Altered metabolism of familial Alzheimer's diseaselinked amyloid precursor protein variants in yeast artificial chromosome transgenic mice. Hum Mol Genet 6: 1535–1541.

    Google Scholar 

  • Lamb BA, Bardel KA, Kulnane LS, Anderson JJ, Holtz G, Wagner SL et al. (1999) Amyloid production and deposition in mutant amyloid precursor protein and presenilin-1 yeast artificial chromosome transgenic mice. Nat Neurosci 2: 695–697.

    Google Scholar 

  • Langford GA, Cozzi E, Yannoutsos N, Lancaster R, Elsome K, Chen P et al. (1996) Production of pigs transgenic for human regulators of complement activation using YAC technology. Transplant Proc 28: 862–863.

    Google Scholar 

  • Lee JT and Jaenisch R (1996) A method for high efficiency YAC lipofection into murine embryonic stem cells. Nucleic Acids Res 24: 5054–5055.

    Google Scholar 

  • Lee JT, Lu N and Han Y (1999) Genetic analysis of the mouse X inactivation center defines an 80-kb multifunction domain. Proc Natl Acad Sci USA 96: 3836–3841.

    Google Scholar 

  • Li Q, Harju S and Peterson KR (1999) Locus control regions: coming of age at a decade plus. Trends Genet 15: 403–408.

    Google Scholar 

  • Li S, Hammer RE, George-Raizen JB, Meyers KC, Garrard WT (2000) High-level rearrangement and transcription of yeast artificial chromosome-based mouse Ig kappa transgenes containing distal regions of the contig. J Immunol 164: 812–824.

    Google Scholar 

  • Linton MF, Farese RV, Jr, Chiesa G, Grass DS, Chin P, Hammer RE et al. (1993) Transgenic mice expressing high plasma concentrations of human apolipoprotein B100 and lipoprotein(a). J Clin Invest 92: 3029–3037.

    Google Scholar 

  • Liu Q, Bungert J and Engel JD (1997) Mutation of gene-proximal regulatory elements disrupts human epsilon-, gamma-, and beta-globin expression in yeast artificial chromosome transgenic mice. Proc Natl Acad Sci USA 94: 169–174.

    Google Scholar 

  • Loring JF, Paszty C, Rose A, McIntosh TK, Murai H, Pierce JE et al. (1996) Rational design of an animal model for Alzheimer's disease: introduction of multiple human genomic transgenes to reproduce AD pathology in a rodent. Neurobiol Aging 17: 173–182.

    Google Scholar 

  • Majumder K, Shawlot W, Schuster G, Harrison W, Elder FF and Overbeek PA (1998) YAC rescue of downless locus mutations in mice. Mamm Genome 9: 863–868.

    Google Scholar 

  • Manson AL, Trezise AE, MacVinish LJ, Kasschau KD, Birchall N, Episkopou V et al. (1997) Complementation of null CF mice with a human CFTR YAC transgene. EMBO J 16: 4238–4249.

    Google Scholar 

  • Matsuura S, Episkopou V, Hamvas R and Brown SD (1996) Xist expression from an Xist YAC transgene carried on the mouse Y chromosome. Hum Mol Genet 5: 451–459.

    Google Scholar 

  • McCormick SP, Ng JK, Taylor S, Flynn LM, Hammer RE and Young SG (1995) Mutagenesis of the human apolipoprotein B gene in a yeast artificial chromosome reveals the site of attachment for apolipoprotein(a). Proc Natl Acad Sci USA 92: 10147–10151.

    Google Scholar 

  • McCormick SP, Ng JK, Cham CM, Taylor S, Marcovina SM, Segrest JP et al. (1997a) Transgenic mice expressing human ApoB95 and ApoB97. Evidence that sequences within the carboxyl-terminal portion of human apoB100 are important for the assembly of lipoprotein. J Biol Chem 272: 23616–23622.

    Google Scholar 

  • McCormick SP, Allan CM, Taylor JM and Young SG (1997b) The use of P1 bacteriophage clones to generate transgenic animals. In: Houdebine LM (ed.) Transgenic Animals, Generation and Use. (pp. 273–281) Harwood Academic Publishers, The Netherlands.

    Google Scholar 

  • McCormick SP and Nielsen LB (1998) Expression of large genomic clones in transgenic mice: new insights into apolipoprotein B structure, function and regulation. Curr Opin Lipidol 9: 103–111.

    Google Scholar 

  • McCreath KJ, Howcroft J, Campbell KHS, Colman A, Schnieke AE and KInd AJ (2000) Production of gene-altered sheep by nuclear transfer from cultured somatic cells. Nature 405: 1066–1069.

    Google Scholar 

  • McKnight RA, Shamay A, Sankaran L, Wall RJ and Hennighausen L (1992) Matrix-attachment regions can impart position-independent regulation of a tissue-specific gene in transgenic mice. Proc Natl Acad Sci USA 89: 6943–6947.

    Google Scholar 

  • Mejia JE and Monaco AP (1997) Retrofitting vectors for Escherichia coli-based artificial chromosomes (PACs and BACs) with markers for transfection studies. Genome Res 7: 179–186.

    Google Scholar 

  • Mendez MJ, Green LL, Corvalan JR, Jia XC, Maynard-Currie, CE, Yang XD et al. (1997) Functional transplant of megabase human immunoglobulin loci recapitulates human antibody response in mice. Nat Genet 15: 146–156.

    Google Scholar 

  • Migeon BR, Kazi E, Haisley-Royster C, Hu J, Reeves R, Call L et al. (1999) Human X inactivation center induces random X chromosome inactivation in male transgenic mice. Genomics 59: 113–121.

    Google Scholar 

  • Monaco AP and Larin Z (1994) YACs, BACs, PACs and MACs: artificial chromosomes as research tools. Trends Biotechnol 12: 280–286.

    Google Scholar 

  • Montoliu L, Schedl A, Kelsey G, Lichter P, Larin Z, Lehrach H et al. (1993) Generation of transgenic mice with yeast artificial chromosomes. Cold Spring Harb Symp Quant Biol 58: 55–62.

    Google Scholar 

  • Montoliu L, Schedl A, Kelsey G, Zentgraf H, Lichter P and Schutz G (1994) Germ line transmission of yeast artificial chromosomes in transgenic mice. Reprod Fertil Dev 6: 577–584.

    Google Scholar 

  • Montoliu L, Bock CT, Schutz G and Zentgraf H (1995) Visualization of large DNA molecules by electron microscopy with polyamines: application to the analysis of yeast endogenous and artificial chromosomes. J Mol Biol 246: 486–492.

    Google Scholar 

  • Montoliu L, Umland T and Schutz G (1996) A locus control region at-12 kb of the tyrosinase gene. EMBO J 15: 6026–6034.

    Google Scholar 

  • Moore AW, Schedl A, McInnes L, Doyle M, Hecksher-Sorensen J and Hastie ND (1998) YAC transgenic analysis reveals Wilms' tumour 1 gene activity in the proliferating coelomic epithelium, developing diaphragm and limb. Mech Dev 79: 169–184.

    Google Scholar 

  • Morgan D, Turnpenny L, Goodship J, Dai W, Majumde K, Matthews L, Gardner A et al. (1998) Inversin, a novel gene in the vertebrate left-right axis pathway, is partially deleted in the inv mouse. Nat Genet 20: 149–156.

    Google Scholar 

  • Mullins LJ, Kotelevtseva N, Boyd AC and Mullins JJ (1997) Efficient Cre-lox linearisation of BACs: applications to physical mapping and generation of transgenic animals. Nucleic Acids Res 25: 2539–2540.

    Google Scholar 

  • Murai H, Pierce JE, Raghupathi R, Smith DH, Saatman KE, Trojanowski JQ et al. (1998) Two-fold overexpression of human beta-amyloid precursor proteins in transgenic mice does not affect the neuromotor, cognitive, or neurodegenerative sequelae following experimental brain injury. J Comp Neurol 392: 428–438.

    Google Scholar 

  • Muyrers JP, Zhang Y, Testa G and Stewart AF (1999) Rapid modification of bacterial artificial chromosomes by ET-recombination. Nucleic Acids Res 27: 1555–1557.

    Google Scholar 

  • Narayanan K, Williamson R, Zhang Y, Stewart AF and Ioannou PA (1999) Efficient and precise engineering of a 200 kb beta-globin human/bacterial artificial chromosome in E. coli DH10B using an inducible homologous recombination system. Gene Ther 6: 442–447.

    Google Scholar 

  • Navas PA, Peterson KR, Li Q, Skarpidi E, Rohde A, Shaw SE et al. (1998) Developmental specificity of the interaction between the locus control region and embryonic or fetal globin genes in transgenic mice with an HS3 core deletion. Mol Cell Biol 18: 4188–4196.

    Google Scholar 

  • Nefedov M, Williamson R and Ioannou PA (2000) Insertion of disease-causing mutations in BACs by homologous recombination in Escherichia coli. Nucleic Acids Res 28: E79.

    Google Scholar 

  • Nielsen LB, McCormick SP, Pierotti V, Tam C, Gunn MD, Shizuya H et al. (1997) Human apolipoprotein B transgenic mice generated with 207-and 145-kilobase pair bacterial artificial chromosomes. Evidence that a distant 5′-element confers appropriate transgene expression in the intestine. J Biol Chem 272: 29752–29758.

    Google Scholar 

  • Nielsen LB, Kahn D, Duell T, Weier HU, Taylor S and Young SG (1998) Apolipoprotein B gene expression in a series of human apolipoprotein B transgenic mice generated with recAassisted endonuclease cleavage-modified bacterial artificial chromosomes. An intestine-specific enhancer element is located between 54 and 62 kilobases 5′ to the structural gene. J Biol Chem 273: 21800–21807.

    Google Scholar 

  • Nielsen LB, McCormick SP and Young SG (1999) A new approach for studying gene regulation by distant DNA elements in transgenic mice. Scand J Clin Lab Invest Suppl 229: 33–39.

    Google Scholar 

  • Orford M, Nefedov M, Vadolas J, Zaibak F, Williamson R and Ioannou PA (2000) Engineering EGFP reporter constructs into a 200 kb human beta-globin BAC clone using GET recombination. Nucleic Acids Res 28: E84.

    Google Scholar 

  • Palmiter RD and Brinster RL (1986). Germ-line transformation of mice. Annu Rev Genet 20: 465–499.

    Google Scholar 

  • Palmiter RD, Sandgren EP, Avarbock MR, Allen DD and Brinster RL (1991) Heterologous introns can enhance expression of transgenes in mice. Proc Natl Acad Sci USA 88: 478–482

    Google Scholar 

  • Palomo C, Zou X, Nicholson IC, Butzler C and Bruggemann M (1999) B-cell tumorigenesis in mice carrying a yeast artificial chromosome-based immunoglobulin heavy/c-myc translocus is independent of the heavy chain intron enhancer (Emu). Cancer Res 59: 5625–5628.

    Google Scholar 

  • Patapoutian A, Miner JH, Lyons GE and Wold B (1993) Isolated sequences from the linked Myf-5 and MRF4 genes drive distinct patterns of muscle-specific expression in transgenic mice. Development 118: 61–69.

    Google Scholar 

  • Payne CM, Mullins LJ and Mullins JJ (1999) Manipulating large genomic clones via in vivo recombination in bacteria. J Hum Hypertens 13: 845–848.

    Google Scholar 

  • Pearson BE and Choi TK (1993) Expression of the human betaamyloid precursor protein gene from a yeast artificial chromosome in transgenic mice. Proc Natl Acad Sci USA 90: 10578–10582.

    Google Scholar 

  • Peterson KR, Clegg CH, Huxley C, Josephson BM, Haugen HS, Furukawa T et al. (1993) Transgenic mice containing a 248-kb yeast artificial chromosome carrying the human beta-globin locus display proper developmental control of human globin genes. Proc Natl Acad Sci USA 90: 7593–7597.

    Google Scholar 

  • Peterson KR, Li QL, Clegg CH, Furukawa T, Navas PA, Norton EJ et al. (1995) Use of yeast artificial chromosomes (YACs) in studies of mammalian development: production of beta-globin locus YAC mice carrying human globin developmental mutants. Proc Natl Acad Sci USA 92: 5655–5659.

    Google Scholar 

  • Peterson KR, Clegg CH, Navas PA, Norton EJ, Kimbrough TG and Stamatoyannopoulos G (1996) Effect of deletion of 5′HS3 or 5′HS2 of the human beta-globin locus control region on the developmental regulation of globin gene expression in beta-globin locus yeast artificial chromosome transgenic mice. Proc Natl Acad Sci USA 93: 6605–6609.

    Google Scholar 

  • Peterson KR (1997a) Production and analysis of transgenic mice containing yeast artificial chromosomes. Genet Eng 19: 235–255.

    Google Scholar 

  • Peterson KR, Clegg CH, Li Q and Stamatoyannopoulos G (1997b) Production of transgenic mice with yeast artificial chromosomes. Trends Genet 13: 61–66.

    Google Scholar 

  • Peterson KR, Navas PA, Li Q and Stamatoyannopoulos G (1998) LCR-dependent gene expression in beta-globin YAC transgenics: detailed structural studies validate functional analysis even in the presence of fragmented YACs. Hum Mol Genet 7: 2079–2088.

    Google Scholar 

  • Peterson KR (1999) Use of yeast artificial chromosomes to express genes in transgenic mice. Methods Enzymol 306: 186–203.

    Google Scholar 

  • Pfeifer K, Leighton PA and Tilghman SM (1996) The structural H19 gene is required for transgene imprinting. Proc Natl Acad Sci USA 93: 13876–13883.

    Google Scholar 

  • Pierce JC, Sauer B and Sternberg N (1992) A positive selection vector for cloning high molecular weight DNA by the bacteriophage P1 system: Improved cloning efficiency. Proc Natl Acad Sci USA 89: 2056–2060.

    Google Scholar 

  • Poorkaj P, Peterson KR and Schellenberg GD (2000) Single-step conversion of P1 and P1 artificial chromosome clones into yeast artificial chromosomes. Genomics 68: 106–110.

    Google Scholar 

  • Porcu S, Kitamura M, Witkowska E, Zhang Z, Mutero A, Lin C et al. (1997) The human beta globin locus introduced by YAC transfer exhibits a specific and reproducible pattern of developmental regulation in transgenic mice. Blood 90: 4602–4609.

    Google Scholar 

  • Probst FJ, Fridell RA, Raphael Y, Saunders TL, Wang A, Liang Y et al. (1998) Correction of deafness in shaker-2 mice by an unconventional myosin in a BAC transgene. Science 280: 1444–1447.

    Google Scholar 

  • Rosenberg C, Florijn RJ, Van de Rijke FM, Blonden LA, Raap TK, Van Ommen GJ et al. (1995) High resolution DNA fiber-fish on yeast artificial chromosomes: direct visualization of DNA replication. Nat Genet 10: 477–479.

    Google Scholar 

  • Rosenberg C, Voltz AK, Lawler AM, Lamb BT, Stetten G and Gearhart JD (1996) Alterations of yeast artificial chromosome transgenic sequences in stretched embryonic stem-cell chromatin visualized by fluorescence in situ hybridization. Cytogenet Cell Genet 75: 67–70.

    Google Scholar 

  • Rouy D, Duverger N, Lin SD, Emmanuel F, Houdebine LM, Denefle P et al. (1998) Apolipoprotein(a) yeast artificial chromosome transgenic rabbits. Lipoprotein(a) assembly with human and rabbit apolipoprotein B. J Biol Chem 273: 1247–1251.

    Google Scholar 

  • Schedl A, Beermann F, Thies E, Montoliu L, Kelsey G and Schutz G (1992) Transgenic mice generated by pronuclear injection of a yeast artificial chromosome. Nucleic Acids Res 20: 3073–3077.

    Google Scholar 

  • Schedl A, Larin Z, Montoliu L, Thies E, Kelsey G, Lehrach H et al. (1993a) A method for the generation of YAC transgenic mice by pronuclear microinjection. Nucleic Acids Res 21: 4783–4787.

    Google Scholar 

  • Schedl A, Montoliu L, Kelsey G and Schutz G (1993b) A yeast artificial chromosome covering the tyrosinase gene confers copy number-dependent expression in transgenic mice. Nature 362: 258–261.

    Google Scholar 

  • Schedl A, Grimes B and Montoliu L (1996a) YAC transfer by microinjection. Methods Mol Biol 54: 293–306.

    Google Scholar 

  • Schedl A, Ross A, Lee M, Engelkamp DPR, van Heyninge V and Hastie ND (1996b) Influence of PAX6 gene dosage on development: overexpression causes severe eye abnormalities. Cell 86: 71–82.

    Google Scholar 

  • Schlessinger D (1990) Yeast artificial chromosomes: tools for mapping and analysis of complex genomes. Trends Genet 6: 248–258.

    Google Scholar 

  • Shizuya H, Birren B, Kim UJ, Mancino V, Slepak T, Tachiiri Y et al. (1992) Cloning and stable maintenance of 300-kilobasepair fragments of human DNA in Escherichia coli using an F-factor-based vector. Proc Natl Acad Sci USA 89: 8794–8797.

    Google Scholar 

  • Sippel AE, Saueressig H, Hubler MC, Faust N and Bonifer C (1997) Insulation of transgenes from chromosomal position effects. In: Houdebine LM (ed.) Transgenic Animals, Generation and Use. (pp. 267–272) Harwood Academic Publishers, The Netherlands.

    Google Scholar 

  • Slee R, Grimes B, Speed RM, Taggart M, Maguire SM, Ross A et al. (1999) A human DAZ transgene confers partial rescue of the mouse Dazl null phenotype. Proc Natl Acad Sci USA 96: 8040–8045.

    Google Scholar 

  • Smith DJ, Zhu Y, Zhang J, Cheng JF and Rubin EM (1995) Construction of a panel of transgenic mice containing a contiguous 2-Mb set of YAC/P1 clones from human chromosome 21q22.2. Genomics 27: 425–434.

    Google Scholar 

  • Smith DJ, Stevens ME, Sudanagunta SP, Bronson RT, Makhinson M, Watabe AM et al. (1997) Functional screening of 2Mb of human chromosome 21q22.2 in transgenic mice implicates minibrain in learning defects associated with Down syndrome. Nat Genet 16: 28–36.

    Google Scholar 

  • Smith DJ and Rubin EM (1997) Functional screening and complex traits: human 21q22.2 sequences affecting learning in mice. Hum Mol Genet 6: 1729–1733.

    Google Scholar 

  • Spencer F, Hugerat Y, Simchen G, Hurko O, Connelly C and Hieter P (1994) Yeast kar1 mutants provide an effective method for YAC transfer to new hosts. Genomics 22: 118–126.

    Google Scholar 

  • Sternberg N, Ruether J and deRiel K (1990) Generation of a 50,000-member human DNA library with an average DNA insert size of 75-100 kb in a bacteriophage P1 cloning vector. New Biol 2: 151–162.

    Google Scholar 

  • Sternberg N (1999) Cloning into bacteriophage P1 vectors. In: Green ED, Birren B, Klapholz S, Myers RM and Hieter P (eds) Genome Analysis. A Laboratory Manual (vol III, Cloning Systems) (pp. 203–239) Cold Spring Harbor Laboratory Press, USA.

    Google Scholar 

  • Stinnakre MG, Soulier S, Schibler L, Lepourry L, Mercier JC and Vilotte JL (1999) Position-independent and copy-numberrelated expression of a goat bacterial artificial chromosome alpha-lactalbumin gene in transgenic mice. Biochem J 339: 33–36.

    Google Scholar 

  • Strauss WM, Dausman J, Beard C, Johnson C, Lawrence JB and Jaenisch R (1993) Germ line transmission of a yeast artificial chromosome spanning the murine alpha 1(I) collagen locus. Science 259: 1904–1907.

    Google Scholar 

  • Symula DJ, Frazer KA, Ueda Y, Denefle P, Stevens ME, Wang ZE et al. (1999) Functional screening of an asthma QTL in YAC transgenic mice. Nat Genet 23: 241–244.

    Google Scholar 

  • Taboit-Dameron F, Malassagne B, Viglietta C, Puissant C, Leroux-Coyau M, Chereau C et al. (1999) Association of the 50HS4 sequence of the chicken beta-globin locus control region with human EF1 alpha gene promoter induces ubiquitous and high expression of human CD55 and CD59 cDNAs in transgenic rabbits. Transgenic Res 8: 223–235.

    Google Scholar 

  • Tanaka S, Yamamoto H, Takeuchi S and Takeuchi T (1990) Melanization in albino mice transformed by introducing cloned mouse tyrosinase gene. Development 108: 223–227.

    Google Scholar 

  • Tanimoto K, Liu Q, Bungert J and Engel JD (1999) Effects of altered gene order or orientation of the locus control region on human beta-globin gene expression in mice. Nature 398: 344–348.

    Google Scholar 

  • Umland T, Montoliu L and Schütz G (1997) The use of yeast artificial chromosomes for transgenesis. In: Houdebine LM (ed.) Transgenic Animals, Generation and Use (pp. 267–272) Harwood Academic Publishers, The Netherlands.

    Google Scholar 

  • Vassaux G and Huxley C (1997) A dicistronic construct allows easy detection of human CFTR expression from YAC DNA in human cells. Nucleic Acids Res 25: 4167–4168.

    Google Scholar 

  • Vassilopoulos G, Navas PA, Skarpidi E, Peterson KR, Lowrey CH, Papayannopoulou T et al. (1999) Correct function of the locus control region may require passage through a nonerythroid cellular environment. Blood 93: 703–712.

    Google Scholar 

  • Wallace H, Ansell R, Clark J and McWhir J (2000) Pre-selection of integration sites imparts repeatable transgene expression. Nucleic Acids Res 28: 1455–1464.

    Google Scholar 

  • Whitelaw CB, Archibald AL, Harris S, McClenaghan M, Simons JP and Clark AJ (1991) Targeting expression to the mammary gland: intronic sequences can enhance the efficiency of gene expression in transgenic mice. Transgenic Res 1: 3–13

    Google Scholar 

  • Wilson C, Bellen HJ and Gehring WJ (1990) Position effects on eukaryotic gene expression. Annu Rev Cell Biol 6: 679–714.

    Google Scholar 

  • Wunderle VM, Critcher R, Hastie N, Goodfellow PN and Schedl A (1998) Deletion of long-range regulatory elements upstream of SOX9 causes campomelic dysplasia. Proc Natl Acad Sci USA 95: 10649–10654.

    Google Scholar 

  • Wutz A, Smrzka OW, Schweifer N, Schellander K, Wagner EF and Barlow DP (1997) Imprinted expression of the Igf2r gene depends on an intronic CpG island. Nature 389: 745–749.

    Google Scholar 

  • Yang XW, Model P and Heintz N (1997) Homologous recombination based modification in Escherichia coli and germline transmission in transgenic mice of a bacterial artificial chromosome. Nat Biotechnol 15: 859–865.

    Google Scholar 

  • Yang XW, Wynder C, Doughty ML and Heintz N (1999) BAC-mediated gene-dosage analysis reveals a role for Zipro1 (Ru49/Zfp38) in progenitor cell proliferation in cerebellum and skin. Nat Genet 22: 327–335.

    Google Scholar 

  • Yannoutsos N, Langford GA, Cozzi E, Lancaster R, Elsome K, Chen P et al. (1995) Production of pigs transgenic for human regulators of complement activation. Transplant Proc 27: 324–325.

    Google Scholar 

  • Yannoutsos N, Ijzermans JN, Harkes C, Bonthuis F, Zhou CY, White D et al. (1996) A membrane cofactor protein transgenic mouse model for the study of discordant xenograft rejection erratum. Genes Cells 1: 409–419.

    Google Scholar 

  • Yu D, Ellis HM, Lee EC, Jenkins NA, Copeland NG and Court DL (2000) An efficient recombination system for chromosome engineering in Escherichia coli. Proc Natl Acad Sci USA 97: 5978–5983.

    Google Scholar 

  • Yu W, Misulovin Z, Suh H, Hardy RR, Jankovic M, Yannoutsos N and Nussenzweig MC (1999) Coordinate regulation of RAG1 and RAG2 by cell type-specific DNA elements 5′ of RAG2. Science 285: 1080–1084.

    Google Scholar 

  • Zhang Y, Buchholz F, Muyrers JP and Stewart AF (1998) A new logic for DNA engineering using recombination in Escherichia coli. Nat Genet 20: 123–128.

    Google Scholar 

  • Zhou Y, Lim KC, Onodera K, Takahashi S, Ohta J, Minegishi N et al. (1998) Rescue of the embryonic lethal hematopoietic defect reveals a critical role for GATA-2 in urogenital development. EMBO J 17: 6689–6700.

    Google Scholar 

  • Zhu Y, Jong MC, Frazer KA, Gong E, Krauss RM, Cheng JF et al. (2000) Genomic interval engineering of mice identifies a novel modulator of triglyceride production. Proc Natl Acad Sci USA 97: 1137–1142.

    Google Scholar 

  • Zou X, Xian J, Davies NP, Popov AV and Bruggemann M (1996) Dominant expression of a 1.3Mb human Ig kappa locus replacing mouse light chain production. FASEB J 10: 1227–1232.

    Google Scholar 

  • Zuelke KA (1998) Transgenic modification of cows milk for valueadded processing. Reprod Fertil Dev 10: 671–676.

    Google Scholar 

  • Zuo J, Treadaway J, Buckner TW and Fritzsch B (1999) Visualization of alpha9 acetylcholine receptor expression in hair cells of transgenic mice containing a modified bacterial artificial chromosome. Proc Natl Acad Sci USA 96: 14100–14105.

    Google Scholar 

  • Zweigerdt R, Braun T and Arnold HH (1997) Faithful expression of the Myf-5 gene during mouse myogenesis requires distant control regions: a transgene approach using yeast artificial chromosomes. Dev Biol 192: 172–180.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Campus de Cantoblanco, 28049, Madrid, Spain

    Patricia Giraldo & Lluís Montoliu

Authors
  1. Patricia Giraldo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lluís Montoliu
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Giraldo, P., Montoliu, L. Size Matters: Use of YACs, BACs and PACs in Transgenic Animals. Transgenic Res 10, 83–103 (2001). https://doi.org/10.1023/A:1008918913249

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1008918913249

Search

Navigation