Current Osteoporosis Reports

, Volume 16, Issue 4, pp 466–477 | Cite as

Mouse Cre Models for the Study of Bone Diseases

  • Sarah L. Dallas
  • Yixia Xie
  • Lora A. Shiflett
  • Yasuyoshi Ueki
Genetics (M Johnson and S Ralston, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Genetics



Transgenic Cre lines are a valuable tool for conditionally inactivating or activating genes to understand their function. Here, we provide an overview of Cre transgenic models used for studying gene function in bone cells and discuss their advantages and limitations, with particular emphasis on Cre lines used for studying osteocyte and osteoclast function.

Recent Findings

Recent studies have shown that many bone cell-targeted Cre models are not as specific as originally thought. To ensure accurate data interpretation, it is important for investigators to test for unexpected recombination events due to transient expression of Cre recombinase during development or in precursor cells and to be aware of the potential for germ line recombination of targeted genes as well as the potential for unexpected phenotypes due to the Cre transgene.


Although many of the bone-targeted Cre-deleter strains are imperfect and each model has its own limitations, their careful use will continue to provide key advances in our understanding of bone cell function in health and disease.


Osteocyte Osteoclast Cre recombinase Conditional knockout Cre-loxP Bone 


Funding Information

SLD was supported by NIH grants P01-AG039355 and R21-AR071563. YU was supported by NIH grants R01-DE025870 and R21-AR070953. YX and LAS were supported by NIH grant P01-AG039355, which also supported the data in Fig. 2.

Compliance with Ethical Standards

Conflict of Interest

Lora Shiflett, Sarah Dallas, Yixia Xie and Yasuyoshi Ueki declare no conflict of interest.

Human and Animal Rights and Informed Consent

All reported studies/experiments with animal subjects performed by the authors have complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).


Papers of particular interest, published recently, have been highlighted as: •• Of major Importance

  1. 1.
    Bivi N, Condon KW, Allen MR, Farlow N, Passeri G, Brun LR, et al. Cell autonomous requirement of connexin 43 for osteocyte survival: consequences for endocortical resorption and periosteal bone formation. J Bone Miner Res. 2012;27(2):374–89. Scholar
  2. 2.
    Xiao Z, Huang J, Cao L, Liang Y, Han X, Quarles LD. Osteocyte-specific deletion of Fgfr1 suppresses FGF23. PLoS One. 2014;9(8):e104154. Scholar
  3. 3.
    Xiong J, Piemontese M, Onal M, Campbell J, Goellner JJ, Dusevich V, et al. Osteocytes, not osteoblasts or lining cells, are the main source of the RANKL required for osteoclast formation in remodeling bone. PLoS One. 2015;10(9):e0138189. Scholar
  4. 4.
    Zhang M, Xuan S, Bouxsein ML, von Stechow D, Akeno N, Faugere MC, et al. Osteoblast-specific knockout of the insulin-like growth factor (IGF) receptor gene reveals an essential role of IGF signaling in bone matrix mineralization. J Biol Chem. 2002;277(46):44005–12. Scholar
  5. 5.
    Zhu M, Sun BH, Saar K, Simpson C, Troiano N, Dallas SL, et al. Deletion of Rac in mature osteoclasts causes Osteopetrosis, an age-dependent change in osteoclast number, and a reduced number of osteoblasts in vivo. J Bone Miner Res. 2016;31(4):864–73. Scholar
  6. 6.
    Balani DH, Ono N, Kronenberg HM. Parathyroid hormone regulates fates of murine osteoblast precursors in vivo. J Clin Invest. 2017;127(9):3327–38. Scholar
  7. 7.
    Liu F, Woitge HW, Braut A, Kronenberg MS, Lichtler AC, Mina M, et al. Expression and activity of osteoblast-targeted Cre recombinase transgenes in murine skeletal tissues. Int J Dev Biol. 2004;48(7):645–53. Scholar
  8. 8.
    Maes C, Kobayashi T, Selig MK, Torrekens S, Roth SI, Mackem S, et al. Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels. Dev Cell. 2010;19(2):329–44. Scholar
  9. 9.
    Song AJ, Palmiter RD. Detecting and avoiding problems when using the Cre-lox system. Trends Genet. 2018;34:333–40. Scholar
  10. 10.
    Bouabe H, Okkenhaug K. Gene targeting in mice: a review. Methods Mol Biol. 2013;1064:315–36. Scholar
  11. 11.
    Sternberg N, Hamilton D. Bacteriophage P1 site-specific recombination. I Recombination between loxP sites. J Mol Biol. 1981;150(4):467–86.CrossRefPubMedGoogle Scholar
  12. 12.
    Dallas SL, Prideaux M, Bonewald LF. The osteocyte: an endocrine cell ... and more. Endocr Rev. 2013;34(5):658–90. Scholar
  13. 13.
    Prideaux M, Findlay DM, Atkins GJ. Osteocytes: the master cells in bone remodelling. Curr Opin Pharmacol. 2016;28:24–30. Scholar
  14. 14.
    Lu Y, Xie Y, Zhang S, Dusevich V, Bonewald LF, Feng JQ. DMP1-targeted Cre expression in odontoblasts and osteocytes. J Dent Res. 2007;86(4):320–5. Scholar
  15. 15.
    Powell WF Jr, Barry KJ, Tulum I, Kobayashi T, Harris SE, Bringhurst FR, et al. Targeted ablation of the PTH/PTHrP receptor in osteocytes impairs bone structure and homeostatic calcemic responses. J Endocrinol. 2011;209(1):21–32. Scholar
  16. 16.
    Javaheri B, Stern AR, Lara N, Dallas M, Zhao H, Liu Y, et al. Deletion of a single beta-catenin allele in osteocytes abolishes the bone anabolic response to loading. J Bone Miner Res. 2014;29(3):705–15. Scholar
  17. 17.
    Kramer I, Halleux C, Keller H, Pegurri M, Gooi JH, Weber PB, et al. Osteocyte Wnt/beta-catenin signaling is required for normal bone homeostasis. Mol Cell Biol. 2010;30(12):3071–85. Scholar
  18. 18.
    Xiong J, Onal M, Jilka RL, Weinstein RS, Manolagas SC, O'Brien CA. Matrix-embedded cells control osteoclast formation. Nat Med. 2011;17(10):1235–41. Scholar
  19. 19.
    Xiong J, Piemontese M, Thostenson JD, Weinstein RS, Manolagas SC, O'Brien CA. Osteocyte-derived RANKL is a critical mediator of the increased bone resorption caused by dietary calcium deficiency. Bone. 2014;66:146–54. Scholar
  20. 20.
    Chen S, Feng J, Bao Q, Li A, Zhang B, Shen Y, et al. Adverse effects of osteocytic constitutive activation of ss-catenin on bone strength and bone growth. J Bone Miner Res. 2015;30(7):1184–94. Scholar
  21. 21.
    Bivi N, Pacheco-Costa R, Brun LR, Murphy TR, Farlow NR, Robling AG, et al. Absence of Cx43 selectively from osteocytes enhances responsiveness to mechanical force in mice. J Orthop Res. 2013;31(7):1075–81. Scholar
  22. 22.
    Kalajzic I, Braut A, Guo D, Jiang X, Kronenberg MS, Mina M, et al. Dentin matrix protein 1 expression during osteoblastic differentiation, generation of an osteocyte GFP-transgene. Bone. 2004;35(1):74–82. Scholar
  23. 23.
    Toyosawa S, Shintani S, Fujiwara T, Ooshima T, Sato A, Ijuhin N, et al. Dentin matrix protein 1 is predominantly expressed in chicken and rat osteocytes but not in osteoblasts. J Bone Miner Res. 2001;16(11):2017–26. Scholar
  24. 24.
    Feng JQ, Huang H, Lu Y, Ye L, Xie Y, Tsutsui TW, et al. The dentin matrix protein 1 (Dmp1) is specifically expressed in mineralized, but not soft, tissues during development. J Dent Res. 2003;82(10):776–80. Scholar
  25. 25.
    •• Kalajzic I, Matthews BG, Torreggiani E, Harris MA, Divieti Pajevic P, Harris SE. In vitro and in vivo approaches to study osteocyte biology. Bone. 2013;54(2):296–306. This article provides an excellent overview of the Dmp1-Cre tissue expression profiles for the 8- and 10-kb Dmp1-Cre and 10kb Dmp1-CreERT2 mouse models and was the first to report off target Cre expression in muscle and some marrow cells. CrossRefPubMedGoogle Scholar
  26. 26.
    Lim J, Burclaff J, He G, Mills JC, Long F. Unintended targeting of Dmp1-Cre reveals a critical role for Bmpr1a signaling in the gastrointestinal mesenchyme of adult mice. Bone Res. 2017;5:16049. Scholar
  27. 27.
    Schmidt-Supprian M, Rajewsky K. Vagaries of conditional gene targeting. Nat Immunol. 2007;8(7):665–8. Scholar
  28. 28.
    Gorski JP, Huffman NT, Vallejo J, Brotto L, Chittur SV, Breggia A, et al. Deletion of Mbtps1 (Pcsk8, S1p, Ski-1) gene in osteocytes stimulates soleus muscle regeneration and increased size and contractile force with age. J Biol Chem. 2016;291(9):4308–22. Scholar
  29. 29.
    Kang KS, Hong JM, Robling AG. Postnatal beta-catenin deletion from Dmp1-expressing osteocytes/osteoblasts reduces structural adaptation to loading, but not periosteal load-induced bone formation. Bone. 2016;88:138–45. Scholar
  30. 30.
    van Bezooijen RL, Roelen BA, Visser A, Van der Wee-Pals L, de Wilt E, Karperien M, et al. Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. J Exp Med. 2004;199(6):805–14. Scholar
  31. 31.
    Maurel D, Johnson ML, SE H, Harris MA, Bonewald LF. Characterization of a new Cre model targeting osteocytes. J Bone Miner Res. 2015;30(Suppl 1):S100.Google Scholar
  32. 32.
    Rodda SJ, McMahon AP. Distinct roles for hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors. Development. 2006;133(16):3231–44. Scholar
  33. 33.
    Rauch A, Seitz S, Baschant U, Schilling AF, Illing A, Stride B, et al. Glucocorticoids suppress bone formation by attenuating osteoblast differentiation via the monomeric glucocorticoid receptor. Cell Metab. 2010;11(6):517–31. Scholar
  34. 34.
    Dacquin R, Starbuck M, Schinke T, Karsenty G. Mouse alpha1(I)-collagen promoter is the best known promoter to drive efficient Cre recombinase expression in osteoblast. Dev Dyn. 2002;224(2):245–51. Scholar
  35. 35.
    Kim JE, Nakashima K, de Crombrugghe B. Transgenic mice expressing a ligand-inducible cre recombinase in osteoblasts and odontoblasts: a new tool to examine physiology and disease of postnatal bone and tooth. Am J Pathol. 2004;165(6):1875–82. Scholar
  36. 36.
    Chen J, Shi Y, Regan J, Karuppaiah K, Ornitz DM, Long F. Osx-Cre targets multiple cell types besides osteoblast lineage in postnatal mice. PLoS One. 2014;9(1):e85161. Scholar
  37. 37.
    •• Huang W, Olsen BR. Skeletal defects in Osterix-Cre transgenic mice. Transgenic Res. 2015;24(1):167–72. This paper showed that there is a skeletal phenotype in the osterix-Cre transgenic mouse without crossing it to a mouse carrying a floxed transgene. This illustrates the need for using controls expressing Osx-Cre or expressing Osx-Cre and heterozygous floxed targeting gene. It also shows that investigators need to be alert for unexpected phenotypes in Cre expressing transgenic mouse lines. CrossRefPubMedGoogle Scholar
  38. 38.
    Wang L, Mishina Y, Liu F. Osterix-Cre transgene causes craniofacial bone development defect. Calcif Tissue Int. 2015;96(2):129–37. Scholar
  39. 39.
    Nakamura T, Imai Y, Matsumoto T, Sato S, Takeuchi K, Igarashi K, et al. Estrogen prevents bone loss via estrogen receptor alpha and induction of Fas ligand in osteoclasts. Cell. 2007;130(5):811–23. Scholar
  40. 40.
    •• Winkeler CL, Kladney RD, Maggi LB Jr, Weber JD. Cathepsin K-Cre causes unexpected germline deletion of genes in mice. PLoS One. 2012;7(7):e42005. This study crossed CatK-Cre mice with Arf floxed mice to delete Arf1 in osteoclasts and unexpectedly observed germline loss of Arf. This was found to be due to expression of Cre in both ovary and testes. This illustrates that investigators need to be alert to potential off-target and/or germline recombination when using Cre transgenic lines. CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Okamoto K, Nakashima T, Shinohara M, Negishi-Koga T, Komatsu N, Terashima A, et al. Osteoimmunology: the conceptual framework unifying the immune and skeletal systems. Physiol Rev. 2017;97(4):1295–349. Scholar
  42. 42.
    Shinohara M, Nakamura M, Masuda H, Hirose J, Kadono Y, Iwasawa M, et al. Class IA phosphatidylinositol 3-kinase regulates osteoclastic bone resorption through protein kinase B-mediated vesicle transport. J Bone Miner Res. 2012;27(12):2464–75. Scholar
  43. 43.
    Saftig P, Hunziker E, Wehmeyer O, Jones S, Boyde A, Rommerskirch W, et al. Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice. Proc Natl Acad Sci U S A. 1998;95(23):13453–8.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Gowen M, Lazner F, Dodds R, Kapadia R, Feild J, Tavaria M, et al. Cathepsin K knockout mice develop osteopetrosis due to a deficit in matrix degradation but not demineralization. J Bone Miner Res. 1999;14(10):1654–63. Scholar
  45. 45.
    Kiviranta R, Morko J, Alatalo SL, NicAmhlaoibh R, Risteli J, Laitala-Leinonen T, et al. Impaired bone resorption in cathepsin K-deficient mice is partially compensated for by enhanced osteoclastogenesis and increased expression of other proteases via an increased RANKL/OPG ratio. Bone. 2005;36(1):159–72. Scholar
  46. 46.
    Li CY, Jepsen KJ, Majeska RJ, Zhang J, Ni R, Gelb BD, et al. Mice lacking cathepsin K maintain bone remodeling but develop bone fragility despite high bone mass. J Bone Miner Res. 2006;21(6):865–75. Scholar
  47. 47.
    Chen W, Yang S, Abe Y, Li M, Wang Y, Shao J, et al. Novel pycnodysostosis mouse model uncovers cathepsin K function as a potential regulator of osteoclast apoptosis and senescence. Hum Mol Genet. 2007;16(4):410–23. Scholar
  48. 48.
    Iwasawa M, Miyazaki T, Nagase Y, Akiyama T, Kadono Y, Nakamura M, et al. The antiapoptotic protein Bcl-xL negatively regulates the bone-resorbing activity of osteoclasts in mice. J Clin Invest. 2009;119(10):3149–59. PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Mizoguchi F, Izu Y, Hayata T, Hemmi H, Nakashima K, Nakamura T, et al. Osteoclast-specific Dicer gene deficiency suppresses osteoclastic bone resorption. J Cell Biochem. 2010;109(5):866–75. Scholar
  50. 50.
    Chiu WS, McManus JF, Notini AJ, Cassady AI, Zajac JD, Davey RA. Transgenic mice that express Cre recombinase in osteoclasts. Genesis. 2004;39(3):178–85. Scholar
  51. 51.
    Sanchez-Fernandez MA, Sbacchi S, Correa-Tapia M, Naumann R, Klemm J, Chambon P, et al. Transgenic mice for a tamoxifen-induced, conditional expression of the Cre recombinase in osteoclasts. PLoS One. 2012;7(5):e37592. Scholar
  52. 52.
    Seeling M, Hillenhoff U, David JP, Schett G, Tuckermann J, Lux A, et al. Inflammatory monocytes and Fcgamma receptor IV on osteoclasts are critical for bone destruction during inflammatory arthritis in mice. Proc Natl Acad Sci U S A. 2013;110(26):10729–34. Scholar
  53. 53.
    Starczak Y, Reinke DC, Barratt KR, Ryan JW, Russell PK, Clarke MV, et al. Absence of vitamin D receptor in mature osteoclasts results in altered osteoclastic activity and bone loss. J Steroid Biochem Mol Biol. 2018;177:77–82. Scholar
  54. 54.
    Sztacho M, Segeletz S, Sanchez-Fernandez MA, Czupalla C, Niehage C, Hoflack B. BAR proteins PSTPIP1/2 regulate podosome dynamics and the resorption activity of osteoclasts. PLoS One. 2016;11(10):e0164829. Scholar
  55. 55.
    Dossa T, Arabian A, Windle JJ, Dedhar S, Teitelbaum SL, Ross FP, et al. Osteoclast-specific inactivation of the integrin-linked kinase (ILK) inhibits bone resorption. J Cell Biochem. 2010;110(4):960–7. Scholar
  56. 56.
    Alanne MH, Siljamaki E, Peltonen S, Vaananen K, Windle JJ, Parada LF, et al. Phenotypic characterization of transgenic mice harboring Nf1+/− or Nf1−/− osteoclasts in otherwise Nf1+/+ background. J Cell Biochem. 2012;113(6):2136–46. Scholar
  57. 57.
    Xie H, Cui Z, Wang L, Xia Z, Hu Y, Xian L, et al. PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis. Nat Med. 2014;20(11):1270–8. Scholar
  58. 58.
    Clausen BE, Burkhardt C, Reith W, Renkawitz R, Forster I. Conditional gene targeting in macrophages and granulocytes using LysMcre mice. Transgenic Res. 1999;8(4):265–77.CrossRefPubMedGoogle Scholar
  59. 59.
    Orthgiess J, Gericke M, Immig K, Schulz A, Hirrlinger J, Bechmann I, et al. Neurons exhibit Lyz2 promoter activity in vivo: implications for using LysM-Cre mice in myeloid cell research. Eur J Immunol. 2016;46(6):1529–32. Scholar
  60. 60.
    Yoshitaka T, Mukai T, Kittaka M, Alford LM, Masrani S, Ishida S, et al. Enhanced TLR-MYD88 signaling stimulates autoinflammation in SH3BP2 cherubism mice and defines the etiology of cherubism. Cell Rep. 2014;8(6):1752–66. Scholar
  61. 61.
    Hume DA. Applications of myeloid-specific promoters in transgenic mice support in vivo imaging and functional genomics but do not support the concept of distinct macrophage and dendritic cell lineages or roles in immunity. J Leukoc Biol. 2011;89(4):525–38. Scholar
  62. 62.
    Aliprantis AO, Ueki Y, Sulyanto R, Park A, Sigrist KS, Sharma SM, et al. NFATc1 in mice represses osteoprotegerin during osteoclastogenesis and dissociates systemic osteopenia from inflammation in cherubism. J Clin Invest. 2008;118(11):3775–89. Scholar
  63. 63.
    Goren I, Allmann N, Yogev N, Schurmann C, Linke A, Holdener M, et al. A transgenic mouse model of inducible macrophage depletion: effects of diphtheria toxin-driven lysozyme M-specific cell lineage ablation on wound inflammatory, angiogenic, and contractive processes. Am J Pathol. 2009;175(1):132–47. Scholar
  64. 64.
    Fukushima H, Shimizu K, Watahiki A, Hoshikawa S, Kosho T, Oba D, et al. NOTCH2 Hajdu-Cheney mutations escape SCF(FBW7)-dependent proteolysis to promote osteoporosis. Mol Cell. 2017;68(4):645–58.e5. Scholar
  65. 65.
    Mass E, Ballesteros I, Farlik M, Halbritter F, Gunther P, Crozet L, et al. Specification of tissue-resident macrophages during organogenesis. Science. 2016;353(6304):aaf4238. Scholar
  66. 66.
    Maeda K, Kobayashi Y, Udagawa N, Uehara S, Ishihara A, Mizoguchi T, et al. Wnt5a-Ror2 signaling between osteoblast-lineage cells and osteoclast precursors enhances osteoclastogenesis. Nat Med. 2012;18(3):405–12. Scholar
  67. 67.
    Nishikawa K, Iwamoto Y, Kobayashi Y, Katsuoka F, Kawaguchi S, Tsujita T, et al. DNA methyltransferase 3a regulates osteoclast differentiation by coupling to an S-adenosylmethionine-producing metabolic pathway. Nat Med. 2015;21(3):281–7. Scholar
  68. 68.
    Yu TY, Pang WJ, Yang GS. Aryl hydrocarbon receptors in osteoclast lineage cells are a negative regulator of bone mass. PLoS One. 2015;10(1):e0117112. Scholar
  69. 69.
    Abram CL, Roberge GL, Hu Y, Lowell CA. Comparative analysis of the efficiency and specificity of myeloid-Cre deleting strains using ROSA-EYFP reporter mice. J Immunol Methods. 2014;408:89–100. Scholar
  70. 70.
    Ishii M, Egen JG, Klauschen F, Meier-Schellersheim M, Saeki Y, Vacher J, et al. Sphingosine-1-phosphate mobilizes osteoclast precursors and regulates bone homeostasis. Nature. 2009;458(7237):524–8. Scholar
  71. 71.
    Sugatani T, Hruska KA. Impaired micro-RNA pathways diminish osteoclast differentiation and function. J Biol Chem. 2009;284(7):4667–78. Scholar
  72. 72.
    Soung do Y, Kalinowski J, Baniwal SK, Jacome-Galarza CE, Frenkel B, Lorenzo J, et al. Runx1-mediated regulation of osteoclast differentiation and function. Mol Endocrinol. 2014;28(4):546–53. Scholar
  73. 73.
    Yuan X, Cao J, Liu T, Li YP, Scannapieco F, He X, et al. Regulators of G protein signaling 12 promotes osteoclastogenesis in bone remodeling and pathological bone loss. Cell Death Differ. 2015;22(12):2046–57. Scholar
  74. 74.
    Ferron M, Vacher J. Targeted expression of Cre recombinase in macrophages and osteoclasts in transgenic mice. Genesis. 2005;41(3):138–45. Scholar
  75. 75.
    Deng L, Zhou JF, Sellers RS, Li JF, Nguyen AV, Wang Y, et al. A novel mouse model of inflammatory bowel disease links mammalian target of rapamycin-dependent hyperproliferation of colonic epithelium to inflammation-associated tumorigenesis. Am J Pathol. 2010;176(2):952–67. Scholar
  76. 76.
    Qian BZ, Li J, Zhang H, Kitamura T, Zhang J, Campion LR, et al. CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature. 2011;475(7355):222–5. Scholar
  77. 77.
    Reddy SV, Hundley JE, Windle JJ, Alcantara O, Linn R, Leach RJ, et al. Characterization of the mouse tartrate-resistant acid phosphatase (TRAP) gene promoter. J Bone Miner Res. 1995;10(4):601–6. CrossRefPubMedGoogle Scholar
  78. 78.
    Luchin A, Suchting S, Merson T, Rosol TJ, Hume DA, Cassady AI, et al. Genetic and physical interactions between Microphthalmia transcription factor and PU.1 are necessary for osteoclast gene expression and differentiation. J Biol Chem. 2001;276(39):36703–10. Scholar
  79. 79.
    Nagashima K, Sawa S, Nitta T, Tsutsumi M, Okamura T, Penninger JM, et al. Identification of subepithelial mesenchymal cells that induce IgA and diversify gut microbiota. Nat Immunol. 2017;18(6):675–82. Scholar
  80. 80.
    Powell JJ, Thomas-McKay E, Thoree V, Robertson J, Hewitt RE, Skepper JN, et al. An endogenous nanomineral chaperones luminal antigen and peptidoglycan to intestinal immune cells. Nat Nanotechnol. 2015;10(4):361–9. Scholar
  81. 81.
    Hanada R, Leibbrandt A, Hanada T, Kitaoka S, Furuyashiki T, Fujihara H, et al. Central control of fever and female body temperature by RANKL/RANK. Nature. 2009;462(7272):505–9. Scholar
  82. 82.
    Kuhn R, Torres RM. Cre/loxP recombination system and gene targeting. Methods Mol Biol. 2002;180:175–204. PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Sarah L. Dallas
    • 1
  • Yixia Xie
    • 1
  • Lora A. Shiflett
    • 1
  • Yasuyoshi Ueki
    • 1
  1. 1.Department of Oral and Craniofacial Sciences, School of DentistryUniversity of MissouriKansasUSA

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