DOI QR코드

DOI QR Code

Mouse Cre-LoxP system: general principles to determine tissue-specific roles of target genes

  • Kim, Hyeonhui (Severance Biomedical Science Institute, Yonsei University College of Medicine) ;
  • Kim, Minki (Severance Biomedical Science Institute, Yonsei University College of Medicine) ;
  • Im, Sun-Kyoung (Severance Biomedical Science Institute, Yonsei University College of Medicine) ;
  • Fang, Sungsoon (Severance Biomedical Science Institute, Yonsei University College of Medicine)
  • Received : 2018.11.08
  • Accepted : 2018.12.05
  • Published : 2018.12.31

Abstract

Genetically engineered mouse models are commonly preferred for studying the human disease due to genetic and pathophysiological similarities between mice and humans. In particular, Cre-loxP system is widely used as an integral experimental tool for generating the conditional. This system has enabled researchers to investigate genes of interest in a tissue/cell (spatial control) and/or time (temporal control) specific manner. A various tissue-specific Cre-driver mouse lines have been generated to date, and new Cre lines are still being developed. This review provides a brief overview of Cre-loxP system and a few commonly used promoters for expression of tissue-specific Cre recombinase. Also, we finally introduce some available links to the Web sites that provides detailed information about Cre mouse lines including their characterization.

Keywords

Acknowledgement

Supported by : National Research Foundation of Korea, Yonsei University College of Medicine

References

  1. Nagy A. Cre recombinase: the universal reagent for genome tailoring. Genesis 2000; 26(2): 99-109. https://doi.org/10.1002/(SICI)1526-968X(200002)26:2<99::AID-GENE1>3.0.CO;2-B
  2. Meinke G, Bohm A, Hauber J, Pisabarro MT, Buchholz F. Cre Recombinase and Other Tyrosine Recombinases. Chem Rev 2016; 116(20): 12785-12820. https://doi.org/10.1021/acs.chemrev.6b00077
  3. Sternberg N, Austin S, Hamilton D, Yarmolinsky M. Analysis of bacteriophage P1 immunity by using lambda-P1 recombinants constructed in vitro. Proc Natl Acad Sci USA 1978; 75(11): 5594-5598. https://doi.org/10.1073/pnas.75.11.5594
  4. Sternberg N, Hamilton D. Bacteriophage P1 site-specific recombination. I. Recombination between loxP sites. J Mol Biol 1981; 150(4): 467-486. https://doi.org/10.1016/0022-2836(81)90375-2
  5. Sternberg N, Sauer B, Hoess R, Abremski K. Bacteriophage P1 cre gene and its regulatory region. Evidence for multiple promoters and for regulation by DNA methylation. J Mol Biol 1986; 187(2): 197-212. https://doi.org/10.1016/0022-2836(86)90228-7
  6. Sauer B. Inducible gene targeting in mice using the Cre/lox system. Methods 1998; 14(4): 381-392. https://doi.org/10.1006/meth.1998.0593
  7. O'Neil KT, Hoess RH, DeGrado WF. Design of DNA-binding peptides based on the leucine zipper motif. Science 1990; 249(4970): 774-778. https://doi.org/10.1126/science.2389143
  8. Sauer B, Henderson N. Site-specific DNA recombination in mammalian cells by the Cre recombinase of bacteriophage P1. Proc Natl Acad Sci USA 1988; 85(14): 5166-5170. https://doi.org/10.1073/pnas.85.14.5166
  9. Branda CS, Dymecki SM. Talking about a revolution: The impact of site-specific recombinases on genetic analyses in mice. Dev Cell 2004; 6(1): 7-28. https://doi.org/10.1016/S1534-5807(03)00399-X
  10. McLellan MA, Rosenthal NA, Pinto AR. Cre-loxP-Mediated Recombination: General Principles and Experimental Considerations. Curr Protoc Mouse Biol 2017; 7(1): 1-12. https://doi.org/10.1002/cpmo.22
  11. Gu H, Zou YR, Rajewsky K. Independent control of immunoglobulin switch recombination at individual switch regions evidenced through Cre-loxP-mediated gene targeting. Cell 1993; 73(6): 1155-1164. https://doi.org/10.1016/0092-8674(93)90644-6
  12. Gu H, Marth JD, Orban PC, Mossmann H, Rajewsky K. Deletion of a DNA polymerase beta gene segment in T cells using cell type-specific gene targeting. Science 1994; 265(5168): 103-106. https://doi.org/10.1126/science.8016642
  13. Rajewsky K, Gu H, Kuhn R, Betz UA, Muller W, Roes J, Schwenk F. Conditional gene targeting. J Clin Invest 1996; 98(3): 600-603. https://doi.org/10.1172/JCI118828
  14. Metzger D, Chambon P. Site- and time-specific gene targeting in the mouse. Methods 2001; 24(1): 71-80. https://doi.org/10.1006/meth.2001.1159
  15. Brocard J, Warot X, Wendling O, Messaddeq N, Vonesch JL, Chambon P, Metzger D. Spatio-temporally controlled site-specific somatic mutagenesis in the mouse. Proc Natl Acad Sci USA 1997; 94(26): 14559-14563. https://doi.org/10.1073/pnas.94.26.14559
  16. Kuhn R, Schwenk F, Aguet M, Rajewsky K. Inducible gene targeting in mice. Science 1995; 269(5229): 1427-1429. https://doi.org/10.1126/science.7660125
  17. Gossen M, Bujard H. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci USA 1992; 89(12): 5547-5551. https://doi.org/10.1073/pnas.89.12.5547
  18. Indra AK, Warot X, Brocard J, Bornert JM, Xiao JH, Chambon P, Metzger D. Temporally-controlled site-specific mutagenesis in the basal layer of the epidermis: comparison of the recombinase activity of the tamoxifen-inducible Cre-ER(T) and Cre-ER(T2) recombinases. Nucleic Acids Res 1999; 27(22): 4324-4327. https://doi.org/10.1093/nar/27.22.4324
  19. Gossen M, Freundlieb S, Bender G, Muller G, Hillen W, Bujard H. Transcriptional activation by tetracyclines in mammalian cells. Science 1995; 268(5218): 1766-1769. https://doi.org/10.1126/science.7792603
  20. Kistner A, Gossen M, Zimmermann F, Jerecic J, Ullmer C, Lubbert H, Bujard H. Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice. Proc Natl Acad Sci USA 1996; 93(20): 10933-10938. https://doi.org/10.1073/pnas.93.20.10933
  21. Gong S, Doughty M, Harbaugh CR, Cummins A, Hatten ME, Heintz N, Gerfen CR. Targeting Cre recombinase to specific neuron populations with bacterial artificial chromosome constructs. J Neurosci 2007; 27(37): 9817-9823. https://doi.org/10.1523/JNEUROSCI.2707-07.2007
  22. Garcia AD, Doan NB, Imura T, Bush TG, Sofroniew MV. GFAPexpressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain. Nat Neurosci 2004; 7(11): 1233-1241. https://doi.org/10.1038/nn1340
  23. Brenner M, Kisseberth WC, Su Y, Besnard F, Messing A. GFAP promoter directs astrocyte-specific expression in transgenic mice. J Neurosci 1994; 14(3 Pt 1): 1030-1037. https://doi.org/10.1523/JNEUROSCI.14-03-01030.1994
  24. Dragatsis I, Zeitlin S. CaMKIIalpha-Cre transgene expression and recombination patterns in the mouse brain. Genesis 2000; 26(2): 133-135. https://doi.org/10.1002/(SICI)1526-968X(200002)26:2<133::AID-GENE10>3.0.CO;2-V
  25. Nakazawa K, Quirk MC, Chitwood RA, Watanabe M, Yeckel MF, Sun LD, Kato A, Carr CA, Johnston D, Wilson MA, Tonegawa S. Requirement for hippocampal CA3 NMDA receptors in associative memory recall. Science 2002; 297(5579): 211-218. https://doi.org/10.1126/science.1071795
  26. Potter GB, Petryniak MA, Shevchenko E, McKinsey GL, Ekker M, Rubenstein JL. Generation of Cre-transgenic mice using Dlx1/Dlx2 enhancers and their characterization in GABAergic interneurons. Mol Cell Neurosci 2009; 40(2): 167-186. https://doi.org/10.1016/j.mcn.2008.10.003
  27. Zerucha T, Stuhmer T, Hatch G, Park BK, Long Q, Yu G, Gambarotta A, Schultz JR, Rubenstein JL, Ekker M. A highly conserved enhancer in the Dlx5/Dlx6 intergenic region is the site of cross-regulatory interactions between Dlx genes in the embryonic forebrain. J Neurosci 2000; 20(2): 709-721. https://doi.org/10.1523/JNEUROSCI.20-02-00709.2000
  28. Monory K, Massa F, Egertova M, Eder M, Blaudzun H, Westenbroek R, Kelsch W, Jacob W, Marsch R, Ekker M, Long J, Rubenstein JL, Goebbels S, Nave KA, During M, Klugmann M, Wolfel B, Dodt HU, Zieglgansberger W, Wotjak CT, Mackie K, Elphick MR, Marsicano G, Lutz B. The endocannabinoid system controls key epileptogenic circuits in the hippocampus. Neuron 2006; 51(4): 455-466. https://doi.org/10.1016/j.neuron.2006.07.006
  29. Taniguchi H, He M, Wu P, Kim S, Paik R, Sugino K, Kvitsiani D, Fu Y, Lu J, Lin Y, Miyoshi G, Shima Y, Fishell G, Nelson SB, Huang ZJ. A resource of Cre driver lines for genetic targeting of GABAergic neurons in cerebral cortex. Neuron 2011; 71(6): 995-1013. https://doi.org/10.1016/j.neuron.2011.07.026
  30. Hippenmeyer S, Vrieseling E, Sigrist M, Portmann T, Laengle C, Ladle DR, Arber S. A developmental switch in the response of DRG neurons to ETS transcription factor signaling. PLoS Biol 2005; 3(5): e159. https://doi.org/10.1371/journal.pbio.0030159
  31. Vong L, Ye C, Yang Z, Choi B, Chua S Jr, Lowell BB. Leptin action on GABAergic neurons prevents obesity and reduces inhibitory tone to POMC neurons. Neuron 2011; 71(1): 142-154. https://doi.org/10.1016/j.neuron.2011.05.028
  32. Tronche F, Kellendonk C, Kretz O, Gass P, Anlag K, Orban PC, Bock R, Klein R, Schutz G. Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety. Nat Genet 1999; 23(1): 99-103. https://doi.org/10.1038/12703
  33. Roesch K, Jadhav AP, Trimarchi JM, Stadler MB, Roska B, Sun BB, Cepko CL. The transcriptome of retinal Muller glial cells. J Comp Neurol 2008; 509(2): 225-238. https://doi.org/10.1002/cne.21730
  34. DeFalco J, Tomishima M, Liu H, Zhao C, Cai X, Marth JD, Enquist L, Friedman JM. Virus-assisted mapping of neural inputs to a feeding center in the hypothalamus. Science 2001; 291(5513): 2608-2613. https://doi.org/10.1126/science.1056602
  35. Doerflinger NH, Macklin WB, Popko B. Inducible site-specific recombination in myelinating cells. Genesis 2003; 35(1): 63-72. https://doi.org/10.1002/gene.10154
  36. Zhang XM, Ng AH, Tanner JA, Wu WT, Copeland NG, Jenkins NA, Huang JD. Highly restricted expression of Cre recombinase in cerebellar Purkinje cells. Genesis 2004; 40(1): 45-51. https://doi.org/10.1002/gene.20062
  37. Zhuang X, Masson J, Gingrich JA, Rayport S, Hen R. Targeted gene expression in dopamine and serotonin neurons of the mouse brain. J Neurosci Methods 2005; 143(1): 27-32. https://doi.org/10.1016/j.jneumeth.2004.09.020
  38. Scott MM, Wylie CJ, Lerch JK, Murphy R, Lobur K, Herlitze S, Jiang W, Conlon RA, Strowbridge BW, Deneris ES. A genetic approach to access serotonin neurons for in vivo and in vitro studies. Proc Natl Acad Sci USA 2005; 102(45): 16472-16477. https://doi.org/10.1073/pnas.0504510102
  39. Chang RB, Strochlic DE, Williams EK, Umans BD, Liberles SD. Vagal Sensory Neuron Subtypes that Differentially Control Breathing. Cell 2015; 161(3): 622-633. https://doi.org/10.1016/j.cell.2015.03.022
  40. Abraira VE, Kuehn ED, Chirila AM, Springel MW, Toliver AA, Zimmerman AL, Orefice LL, Boyle KA, Bai L, Song BJ, Bashista KA, O'Neill TG, Zhuo J, Tsan C, Hoynoski J, Rutlin M, Kus L, Niederkofler V, Watanabe M, Dymecki SM, Nelson SB, Heintz N, Hughes DI, Ginty DD. The Cellular and Synaptic Architecture of the Mechanosensory Dorsal Horn. Cell 2017; 168(1-2): 295-310. https://doi.org/10.1016/j.cell.2016.12.010
  41. Hasegawa H, Abbott S, Han BX, Qi Y, Wang F. Analyzing somatosensory axon projections with the sensory neuron-specific Advillin gene. J Neurosci 2007; 27(52): 14404-14414. https://doi.org/10.1523/JNEUROSCI.4908-07.2007
  42. Lau J, Minett MS, Zhao J, Dennehy U, Wang F, Wood JN, Bogdanov YD. Temporal control of gene deletion in sensory ganglia using a tamoxifen-inducible Advillin-Cre-ERT2 recombinase mouse. Mol Pain 2011; 7: 100.
  43. Lewis AE, Vasudevan HN, O'Neill AK, Soriano P, Bush JO. The widely used Wnt1-Cre transgene causes developmental phenotypes by ectopic activation of Wnt signaling. Dev Biol 2013; 379(2): 229-234. https://doi.org/10.1016/j.ydbio.2013.04.026
  44. Minett MS, Nassar MA, Clark AK, Passmore G, Dickenson AH, Wang F, Malcangio M, Wood JN. Distinct Nav1.7-dependent pain sensations require different sets of sensory and sympathetic neurons. Nat Commun 2012; 3(1): 791. https://doi.org/10.1038/ncomms1795
  45. Zhou X, Wang L, Hasegawa H, Amin P, Han BX, Kaneko S, He Y, Wang F. Deletion of PIK3C3/Vps34 in sensory neurons causes rapid neurodegeneration by disrupting the endosomal but not the autophagic pathway. Proc Natl Acad Sci USA 2010; 107(20): 9424-9429. https://doi.org/10.1073/pnas.0914725107
  46. Simpson CL, Patel DM, Green KJ. Deconstructing the skin: cytoarchitectural determinants of epidermal morphogenesis. Nat Rev Mol Cell Biol 2011; 12(9): 565-580. https://doi.org/10.1038/nrm3175
  47. Dassule HR, Lewis P, Bei M, Maas R, McMahon AP. Sonic hedgehog regulates growth and morphogenesis of the tooth. Development 2000; 127(22): 4775-4785.
  48. Calleja C, Messaddeq N, Chapellier B, Yang H, Krezel W, Li M, Metzger D, Mascrez B, Ohta K, Kagechika H, Endo Y, Mark M, Ghyselinck NB, Chambon P. Genetic and pharmacological evidence that a retinoic acid cannot be the RXR-activating ligand in mouse epidermis keratinocytes. Genes Dev 2006; 20(11): 1525-1538. https://doi.org/10.1101/gad.368706
  49. Van Keymeulen A, Mascre G, Youseff KK, Harel I, Michaux C, De Geest N, Szpalski C, Achouri Y, Bloch W, Hassan BA, Blanpain C. Epidermal progenitors give rise to Merkel cells during embryonic development and adult homeostasis. J Cell Biol 2009; 187(1): 91-100. https://doi.org/10.1083/jcb.200907080
  50. Snippert HJ, Haegebarth A, Kasper M, Jaks V, van Es JH, Barker N, van de Wetering M, van den Born M, Begthel H, Vries RG, Stange DE, Toftgard R, Clevers H. Lgr6 marks stem cells in the hair follicle that generate all cell lineages of the skin. Science 2010; 327(5971): 1385-1389. https://doi.org/10.1126/science.1184733
  51. Gasteiger G, Rudensky AY. Interactions between innate and adaptive lymphocytes. Nat Rev Immunol 2014; 14(9): 631-639. https://doi.org/10.1038/nri3726
  52. Tomar N, De RK. A brief outline of the immune system. Methods Mol Biol 2014; 1184: 3-12.
  53. Huston DP. The biology of the immune system. JAMA 1997; 278(22): 1804-1814. https://doi.org/10.1001/jama.1997.03550220010004
  54. 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): 265-277. https://doi.org/10.1023/A:1008942828960
  55. Caton ML, Smith-Raska MR, Reizis B. Notch-RBP-J signaling controls the homeostasis of CD8- dendritic cells in the spleen. J Exp Med 2007; 204(7): 1653-1664. https://doi.org/10.1084/jem.20062648
  56. Musch W, Wege AK, Mannel DN, Hehlgans T. Generation and characterization of alpha-chymase-Cre transgenic mice. Genesis 2008; 46(3): 163-166. https://doi.org/10.1002/dvg.20378
  57. Vacchio MS, Wang L, Bouladoux N, Carpenter AC, Xiong Y, Williams LC, Wohlfert E, Song KD, Belkaid Y, Love PE, Bosselut R. A ThPOK-LRF transcriptional node maintains the integrity and effector potential of post-thymic CD4+ T cells. Nat Immunol 2014; 15(10): 947-956. https://doi.org/10.1038/ni.2960
  58. Sawada S, Scarborough JD, Killeen N, Littman DR. A lineagespecific transcriptional silencer regulates CD4 gene expression during T lymphocyte development. Cell 1994; 77(6): 917-929. https://doi.org/10.1016/0092-8674(94)90140-6
  59. Lee PP, Fitzpatrick DR, Beard C, Jessup HK, Lehar S, Makar KW, Perez-Melgosa M, Sweetser MT, Schlissel MS, Nguyen S, Cherry SR, Tsai JH, Tucker SM, Weaver WM, Kelso A, Jaenisch R, Wilson CB. A critical role for Dnmt1 and DNA methylation in T cell development, function, and survival. Immunity 2001; 15(5): 763-774. https://doi.org/10.1016/S1074-7613(01)00227-8
  60. Klinger M, Kim JK, Chmura SA, Barczak A, Erle DJ, Killeen N. Thymic OX40 expression discriminates cells undergoing strong responses to selection ligands. J Immunol 2009; 182(8): 4581-4589. https://doi.org/10.4049/jimmunol.0900010
  61. Maekawa Y, Minato Y, Ishifune C, Kurihara T, Kitamura A, Kojima H, Yagita H, Sakata-Yanagimoto M, Saito T, Taniuchi I, Chiba S, Sone S, Yasutomo K. Notch2 integrates signaling by the transcription factors RBP-J and CREB1 to promote T cell cytotoxicity. Nat Immunol 2008; 9(10): 1140-1147. https://doi.org/10.1038/ni.1649
  62. Rubtsov YP, Niec RE, Josefowicz S, Li L, Darce J, Mathis D, Benoist C, Rudensky AY. Stability of the regulatory T cell lineage in vivo. Science 2010; 329(5999): 1667-1671. https://doi.org/10.1126/science.1191996
  63. Hennet T, Hagen FK, Tabak LA, Marth JD. T-cell-specific deletion of a polypeptide N-acetylgalactosaminyl-transferase gene by site-directed recombination. Proc Natl Acad Sci USA 1995; 92(26): 12070-12074. https://doi.org/10.1073/pnas.92.26.12070
  64. Wang Q, Strong J, Killeen N. Homeostatic competition among T cells revealed by conditional inactivation of the mouse Cd4 gene. J Exp Med 2001; 194(12): 1721-1730. https://doi.org/10.1084/jem.194.12.1721
  65. Rickert RC, Roes J, Rajewsky K. B lymphocyte-specific, Cremediated mutagenesis in mice. Nucleic Acids Res 1997; 25(6): 1317-1318. https://doi.org/10.1093/nar/25.6.1317
  66. Yasuda T, Wirtz T, Zhang B, Wunderlich T, Schmidt-Supprian M, Sommermann T, Rajewsky K. Studying Epstein-Barr virus pathologies and immune surveillance by reconstructing EBV infection in mice. Cold Spring Harb Symp Quant Biol 2013; 78: 259-263. https://doi.org/10.1101/sqb.2013.78.020222
  67. Ogilvy S, Elefanty AG, Visvader J, Bath ML, Harris AW, Adams JM. Transcriptional regulation of vav, a gene expressed throughout the hematopoietic compartment. Blood 1998; 91(2): 419-430. https://doi.org/10.1182/blood.V91.2.419
  68. Ogilvy S, Metcalf D, Gibson L, Bath ML, Harris AW, Adams JM. Promoter elements of vav drive transgene expression in vivo throughout the hematopoietic compartment. Blood 1999; 94(6): 1855-1863. https://doi.org/10.1182/blood.V94.6.1855
  69. Shimshek DR, Kim J, Hubner MR, Spergel DJ, Buchholz F, Casanova E, Stewart AF, Seeburg PH, Sprengel R. Codonimproved Cre recombinase (iCre) expression in the mouse. Genesis 2002; 32(1): 19-26. https://doi.org/10.1002/gene.10023
  70. Yang J, Hills D, Taylor E, Pfeffer K, Ure J, Medvinsky A. Transgenic tools for analysis of the haematopoietic system: knock-in CD45 reporter and deletor mice. J Immunol Methods 2008; 337(2): 81-87. https://doi.org/10.1016/j.jim.2008.06.001
  71. Sosiæ D, Richardson JA, Yu K, Ornitz DM, Olson EN. Twist regulates cytokine gene expression through a negative feedback loop that represses NF-kappaB activity. Cell 2003; 112(2): 169-180. https://doi.org/10.1016/S0092-8674(03)00002-3
  72. Yu K, Xu J, Liu Z, Sosic D, Shao J, Olson EN, Towler DA, Ornitz DM. Conditional inactivation of FGF receptor 2 reveals an essential role for FGF signaling in the regulation of osteoblast function and bone growth. Development 2003; 130(13): 3063-3074. https://doi.org/10.1242/dev.00491
  73. Logan M, Martin JF, Nagy A, Lobe C, Olson EN, Tabin CJ. Expression of Cre Recombinase in the developing mouse limb bud driven by a Prxl enhancer. Genesis 2002; 33(2): 77-80. https://doi.org/10.1002/gene.10092
  74. Zhang M, Xuan S, Bouxsein ML, von Stechow D, Akeno N, Faugere MC, Malluche H, Zhao G, Rosen CJ, Efstratiadis A, Clemens TL. 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): 44005-44012. https://doi.org/10.1074/jbc.M208265200
  75. 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): 1875-1882. https://doi.org/10.1016/S0002-9440(10)63240-3
  76. Rodda SJ, McMahon AP. Distinct roles for Hedgehog and canonical Wnt signaling in specification, differentiation and maintenance of osteoblast progenitors. Development 2006; 133(16): 3231-3244. https://doi.org/10.1242/dev.02480
  77. 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): 320-325. https://doi.org/10.1177/154405910708600404
  78. Baek WY, de Crombrugghe B, Kim JE. Postnatally induced inactivation of Osterix in osteoblasts results in the reduction of bone formation and maintenance. Bone 2010; 46(4): 920-928. https://doi.org/10.1016/j.bone.2009.12.007
  79. Sanchez-Fernandez MA, Sbacchi S, Correa-Tapia M, Naumann R, Klemm J, Chambon P, Al-Robaiy S, Blessing M, Hoflack B. Transgenic mice for a tamoxifen-induced, conditional expression of the Cre recombinase in osteoclasts. PLoS One 2012; 7(5): e37592. https://doi.org/10.1371/journal.pone.0037592
  80. Tonna S, Takyar FM, Vrahnas C, Crimeen-Irwin B, Ho PW, Poulton IJ, Brennan HJ, McGregor NE, Allan EH, Nguyen H, Forwood MR, Tatarczuch L, Mackie EJ, Martin TJ, Sims NA. EphrinB2 signaling in osteoblasts promotes bone mineralization by preventing apoptosis. FASEB J 2014; 28(10): 4482-4496. https://doi.org/10.1096/fj.14-254300
  81. Henry SP, Jang CW, Deng JM, Zhang Z, Behringer RR, de Crombrugghe B. Generation of aggrecan-CreERT2 knockin mice for inducible Cre activity in adult cartilage. Genesis 2009; 47(12): 805-814. https://doi.org/10.1002/dvg.20564
  82. Gebhard S, Hattori T, Bauer E, Schlund B, Bosl MR, de Crombrugghe B, von der Mark K. Specific expression of Cre recombinase in hypertrophic cartilage under the control of a BAC-Col10a1 promoter. Matrix Biol 2008; 27(8): 693-699. https://doi.org/10.1016/j.matbio.2008.07.001
  83. Maye P, Fu Y, Butler DL, Chokalingam K, Liu Y, Floret J, Stover ML, Wenstrup R, Jiang X, Gooch C, Rowe D. Generation and characterization of Col10a1-mcherry reporter mice. Genesis 2011; 49(5): 410-418. https://doi.org/10.1002/dvg.20733
  84. Miniou P, Tiziano D, Frugier T, Roblot N, Le Meur M, Melki J. Gene targeting restricted to mouse striated muscle lineage. Nucleic Acids Res 1999; 27(19): e27. https://doi.org/10.1093/nar/27.19.e27
  85. Tallquist MD, Weismann KE, Hellstrom M, Soriano P. Early myotome specification regulates PDGFA expression and axial skeleton development. Development 2000; 127(23): 5059-5070.
  86. Keller C, Arenkiel BR, Coffin CM, El-Bardeesy N, DePinho RA, Capecchi MR. Alveolar rhabdomyosarcomas in conditional Pax3:Fkhr mice: cooperativity of Ink4a/ARF and Trp53 loss of function. Genes Dev 2004; 18(21): 2614-2626. https://doi.org/10.1101/gad.1244004
  87. Bruning JC, Michael MD, Winnay JN, Hayashi T, Horsch D, Accili D, Goodyear LJ, Kahn CR. A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol Cell 1998; 2(5): 559-569. https://doi.org/10.1016/S1097-2765(00)80155-0
  88. Boucher P, Gotthardt M, Li WP, Anderson RG, Herz J. LRP: role in vascular wall integrity and protection from atherosclerosis. Science 2003; 300(5617): 329-332. https://doi.org/10.1126/science.1082095
  89. Nakagawa H, Wang TC, Zukerberg L, Odze R, Togawa K, May GH, Wilson J, Rustgi AK. The targeting of the cyclin D1 oncogene by an Epstein-Barr virus promoter in transgenic mice causes dysplasia in the tongue, esophagus and forestomach. Oncogene 1997; 14(10): 1185-1190. https://doi.org/10.1038/sj.onc.1200937
  90. Andl CD, Mizushima T, Nakagawa H, Oyama K, Harada H, Chruma K, Herlyn M, Rustgi AK. Epidermal growth factor receptor mediates increased cell proliferation, migration, and aggregation in esophageal keratinocytes in vitro and in vivo. J Biol Chem 2003; 278(3): 1824-1830. https://doi.org/10.1074/jbc.M209148200
  91. Tetreault MP, Yang Y, Travis J, Yu QC, Klein-Szanto A, Tobias JW, Katz JP. Esophageal squamous cell dysplasia and delayed differentiation with deletion of kruppel-like factor 4 in murine esophagus. Gastroenterology 2010; 139(1): 171-181. https://doi.org/10.1053/j.gastro.2010.03.048
  92. Syder AJ, Karam SM, Mills JC, Ippolito JE, Ansari HR, Farook V, Gordon JI. A transgenic mouse model of metastatic carcinoma involving transdifferentiation of a gastric epithelial lineage progenitor to a neuroendocrine phenotype. Proc Natl Acad Sci USA 2004; 101(13): 4471-4476. https://doi.org/10.1073/pnas.0307983101
  93. Engevik AC, Feng R, Yang L, Zavros Y. The acid-secreting parietal cell as an endocrine source of Sonic Hedgehog during gastric repair. Endocrinology 2013; 154(12): 4627-4639. https://doi.org/10.1210/en.2013-1483
  94. Thiem S, Eissmann MF, Stuart E, Elzer J, Jonas A, Buchert M, Ernst M. Inducible gene modification in the gastric epithelium of Tff1-CreERT2, Tff2-rtTA, Tff3-luc mice. Genesis 2016; 54(12): 626-635. https://doi.org/10.1002/dvg.22987
  95. Xue Y, Johnson R, Desmet M, Snyder PW, Fleet JC. Generation of a transgenic mouse for colorectal cancer research with intestinal cre expression limited to the large intestine. Mol Cancer Res 2010; 8(8): 1095-1104. https://doi.org/10.1158/1541-7786.MCR-10-0195
  96. Madison BB, Dunbar L, Qiao XT, Braunstein K, Braunstein E, Gumucio DL. Cis elements of the villin gene control expression in restricted domains of the vertical (crypt) and horizontal (duodenum, cecum) axes of the intestine. J Biol Chem 2002; 277(36): 33275-33283. https://doi.org/10.1074/jbc.M204935200
  97. Bullard T, Koek L, Roztocil E, Kingsley PD, Mirels L, Ovitt CE. Ascl3 expression marks a progenitor population of both acinar and ductal cells in mouse salivary glands. Dev Biol 2008; 320(1): 72-78. https://doi.org/10.1016/j.ydbio.2008.04.018
  98. Yakar S, Liu JL, Stannard B, Butler A, Accili D, Sauer B, LeRoith D. Normal growth and development in the absence of hepatic insulin-like growth factor I. Proc Natl Acad Sci USA 1999; 96(13): 7324-7329. https://doi.org/10.1073/pnas.96.13.7324
  99. Stratikopoulos E, Szabolcs M, Dragatsis I, Klinakis A, Efstratiadis A. The hormonal action of IGF1 in postnatal mouse growth. Proc Natl Acad Sci USA 2008; 105(49): 19378-19383. https://doi.org/10.1073/pnas.0809223105
  100. Shiota C, Prasadan K, Guo P, Fusco J, Xiao X, Gittes GK. GcgCreERT2 knockin mice as a tool for genetic manipulation in pancreatic alpha cells. Diabetologia 2017; 60(12): 2399-2408. https://doi.org/10.1007/s00125-017-4425-x
  101. Herrera PL, Orci L, Vassalli JD. Two transgenic approaches to define the cell lineages in endocrine pancreas development. Mol Cell Endocrinol 1998; 140(1-2): 45-50. https://doi.org/10.1016/S0303-7207(98)00028-8
  102. Arnes L, Hill JT, Gross S, Magnuson MA, Sussel L. Ghrelin expression in the mouse pancreas defines a unique multipotent progenitor population. PLoS One 2012; 7(12): e52026. https://doi.org/10.1371/journal.pone.0052026
  103. Thorens B, Tarussio D, Maestro MA, Rovira M, Heikkila E, Ferrer J. Ins1(Cre) knock-in mice for beta cell-specific gene recombination. Diabetologia 2015; 58(3): 558-565. https://doi.org/10.1007/s00125-014-3468-5
  104. Postic C, Shiota M, Niswender KD, Jetton TL, Chen Y, Moates JM, Shelton KD, Lindner J, Cherrington AD, Magnuson MA. Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic beta cell-specific gene knock-outs using Cre recombinase. J Biol Chem 1999; 274(1): 305-315. https://doi.org/10.1074/jbc.274.1.305
  105. Kopinke D, Brailsford M, Pan FC, Magnuson MA, Wright CV, Murtaugh LC. Ongoing Notch signaling maintains phenotypic fidelity in the adult exocrine pancreas. Dev Biol 2012; 362(1): 57-64. https://doi.org/10.1016/j.ydbio.2011.11.010
  106. Kopp JL, Dubois CL, Schaffer AE, Hao E, Shih HP, Seymour PA, Ma J, Sander M. Sox9+ ductal cells are multipotent progenitors throughout development but do not produce new endocrine cells in the normal or injured adult pancreas. Development 2011; 138(4): 653-665. https://doi.org/10.1242/dev.056499
  107. Ayala de la Pena F, Kanasaki K, Kanasaki M, Tangirala N, Maeda G, Kalluri R. Loss of p53 and acquisition of angiogenic microRNA profile are insufficient to facilitate progression of bladder urothelial carcinoma in situ to invasive carcinoma. J Biol Chem 2011; 286(23): 20778-20787. https://doi.org/10.1074/jbc.M110.198069
  108. Ge Y, Ahn D, Stricklett PK, Hughes AK, Yanagisawa M, Verbalis JG, Kohan DE. Collecting duct-specific knockout of endothelin-1 alters vasopressin regulation of urine osmolality. Am J Physiol Renal Physiol 2005; 288(5): F912-920. https://doi.org/10.1152/ajprenal.00432.2004
  109. Humphreys BD, Lin SL, Kobayashi A, Hudson TE, Nowlin BT, Bonventre JV, Valerius MT, McMahon AP, Duffield JS. Fate tracing reveals the pericyte and not epithelial origin of myofibroblasts in kidney fibrosis. Am J Pathol 2010; 176(1): 85-97. https://doi.org/10.2353/ajpath.2010.090517
  110. Cebrian C, Asai N, D'Agati V, Costantini F. The number of fetal nephron progenitor cells limits ureteric branching and adult nephron endowment. Cell Rep 2014; 7(1): 127-137. https://doi.org/10.1016/j.celrep.2014.02.033
  111. Iwano M, Plieth D, Danoff TM, Xue C, Okada H, Neilson EG. Evidence that fibroblasts derive from epithelium during tissue fibrosis. J Clin Invest 2002; 110(3): 341-350. https://doi.org/10.1172/JCI0215518
  112. Li H, Zhou X, Davis DR, Xu D, Sigmund CD. An androgeninducible proximal tubule-specific Cre recombinase transgenic model. Am J Physiol Renal Physiol 2008; 294(6): F1481-1486. https://doi.org/10.1152/ajprenal.00064.2008
  113. Moeller MJ, Sanden SK, Soofi A, Wiggins RC, Holzman LB. Podocyte-specific expression of cre recombinase in transgenic mice. Genesis 2003; 35(1): 39-42. https://doi.org/10.1002/gene.10164
  114. Lan ZJ, Xu X, Cooney AJ. Differential oocyte-specific expression of Cre recombinase activity in GDF-9-iCre, Zp3cre, and Msx2Cre transgenic mice. Biol Reprod 2004; 71(5): 1469-1474. https://doi.org/10.1095/biolreprod.104.031757
  115. Lewandoski M, Wassarman KM, Martin GR. Zp3-cre, a transgenic mouse line for the activation or inactivation of loxPflanked target genes specifically in the female germ line. Curr Biol 1997; 7(2): 148-151. https://doi.org/10.1016/S0960-9822(06)00059-5
  116. de Vries WN, Binns LT, Fancher KS, Dean J, Moore R, Kemler R, Knowles BB. Expression of Cre recombinase in mouse oocytes: a means to study maternal effect genes. Genesis 2000; 26(2): 110-112. https://doi.org/10.1002/(SICI)1526-968X(200002)26:2<110::AID-GENE2>3.0.CO;2-8
  117. Holdcraft RW, Braun RE. Androgen receptor function is required in Sertoli cells for the terminal differentiation of haploid spermatids. Development 2004; 131(2): 459-467.
  118. Inselman AL, Nakamura N, Brown PR, Willis WD, Goulding EH, Eddy EM. Heat shock protein 2 promoter drives Cre expression in spermatocytes of transgenic mice. Genesis 2010; 48(2): 114-120. https://doi.org/10.1002/dvg.20588
  119. Smedley D, Salimova E, Rosenthal N. Cre recombinase resources for conditional mouse mutagenesis. Methods 2011; 53(4): 411-416. https://doi.org/10.1016/j.ymeth.2010.12.027
  120. Chandras C, Zouberakis M, Salimova E, Smedley D, Rosenthal N, Aidinis V. CreZOO--the European virtual repository of Cre and other targeted conditional driver strains. Database (Oxford) 2012; 2012: bas029.
  121. Murray SA, Eppig JT, Smedley D, Simpson EM, Rosenthal N. Beyond knockouts: cre resources for conditional mutagenesis. Mamm Genome 2012; 23(9-10): 587-599. https://doi.org/10.1007/s00335-012-9430-2
  122. Schofield PN, Hoehndorf R, Gkoutos GV. Mouse genetic and phenotypic resources for human genetics. Hum Mutat 2012; 33(5): 826-836. https://doi.org/10.1002/humu.22077
  123. Sung YH, Baek IJ, Seong JK, Kim JS, Lee HW. Mouse genetics: catalogue and scissors. BMB Rep 2012; 45(12): 686-692. https://doi.org/10.5483/BMBRep.2012.45.12.242
  124. Sharma S, Zhu J. Immunologic applications of conditional gene modification technology in the mouse. Curr Protoc Immunol 2014; 105: 1-13.
  125. Tsien JZ. Cre-Lox Neurogenetics: 20 Years of Versatile Applications in Brain Research and Counting. Front Genet 2016; 7: 19.
  126. Kersten K, de Visser KE, van Miltenburg MH, Jonkers J. Genetically engineered mouse models in oncology research and cancer medicine. EMBO Mol Med 2017; 9(2): 137-153. https://doi.org/10.15252/emmm.201606857
  127. Gong S, Kus L, Heintz N. Rapid bacterial artificial chromosome modification for large-scale mouse transgenesis. Nat Protoc 2010; 5(10): 1678-1696. https://doi.org/10.1038/nprot.2010.131

Cited by

  1. Targeting cancer stem cells in squamous cell carcinoma vol.2, pp.3, 2018, https://doi.org/10.1093/pcmedi/pbz016
  2. Breast cancer animal models and applications vol.41, pp.5, 2020, https://doi.org/10.24272/j.issn.2095-8137.2020.095
  3. Generation of PECAM‐1 (CD31) conditional knockout mice vol.58, pp.2, 2018, https://doi.org/10.1002/dvg.23346
  4. Establishment of a conditional Nomo1 mouse model by CRISPR/Cas9 technology vol.47, pp.2, 2018, https://doi.org/10.1007/s11033-019-05214-7
  5. Placental gene editing via trophectoderm-specific Tat-Cre/loxP recombination vol.147, pp.13, 2020, https://doi.org/10.1242/dev.190371
  6. Characterization of Anaphylatoxin Receptor Expression and C3a/C5a Functions in Anaphylatoxin Receptor Reporter Mice vol.130, pp.1, 2018, https://doi.org/10.1002/cpim.100
  7. Molecular Biological Aspects of Depressive Disorders: A Modern View vol.54, pp.5, 2018, https://doi.org/10.1134/s0026893320050118
  8. Small-molecule inducible transcriptional control in mammalian cells vol.40, pp.8, 2018, https://doi.org/10.1080/07388551.2020.1808583
  9. Optimization of tamoxifen-induced Cre activity and its effect on immune cell populations vol.10, pp.1, 2020, https://doi.org/10.1038/s41598-020-72179-0
  10. JF1/B6F1 Ngly1−/− mouse as an isogenic animal model of NGLY1 deficiency vol.97, pp.2, 2018, https://doi.org/10.2183/pjab.97.005
  11. Photoactivatable Cre knock-in mice for spatiotemporal control of genetic engineering in vivo vol.101, pp.1, 2018, https://doi.org/10.1038/s41374-020-00482-5
  12. Utility of progesterone receptor‐ires‐Cre to generate conditional knockout mice for uterine study vol.92, pp.1, 2021, https://doi.org/10.1111/asj.13615
  13. Advances in Genome Editing and Application to the Generation of Genetically Modified Rat Models vol.12, pp.None, 2018, https://doi.org/10.3389/fgene.2021.615491
  14. Two-Way Development of the Genetic Model for Endometrial Tumorigenesis in Mice: Current and Future Perspectives vol.12, pp.None, 2018, https://doi.org/10.3389/fgene.2021.798628
  15. Deficits Associated With Loss of STIM1 in Purkinje Neurons Including Motor Coordination Can Be Rescued by Loss of Septin 7 vol.9, pp.None, 2018, https://doi.org/10.3389/fcell.2021.794807
  16. Cell Lineage Infidelity in PDAC Progression and Therapy Resistance vol.9, pp.None, 2021, https://doi.org/10.3389/fcell.2021.795251
  17. Molecular Interactions Between Vascular Smooth Muscle Cells and Macrophages in Atherosclerosis vol.8, pp.None, 2018, https://doi.org/10.3389/fcvm.2021.737934
  18. A Review of the Current State of Nanomedicines for Targeting and Treatment of Cancers: Achievements and Future Challenges vol.4, pp.2, 2021, https://doi.org/10.1002/adtp.202000186
  19. Autophagy in the cancer-immunity dialogue vol.169, pp.None, 2018, https://doi.org/10.1016/j.addr.2020.12.003
  20. RhoA- and Actin-Dependent Functions of Macrophages from the Rodent Cardiac Transplantation Model Perspective -Timing Is the Essence vol.10, pp.2, 2021, https://doi.org/10.3390/biology10020070
  21. The Missing Link: Cre Pigs for Cancer Research vol.11, pp.None, 2021, https://doi.org/10.3389/fonc.2021.755746
  22. Mouse Models of Peritoneal Carcinomatosis to Develop Clinical Applications vol.13, pp.5, 2018, https://doi.org/10.3390/cancers13050963
  23. Genetically Encoded Fluorescent Indicators for Imaging Brain Chemistry vol.11, pp.4, 2018, https://doi.org/10.3390/bios11040116
  24. Recent Advances in Implantation-Based Genetic Modeling of Biliary Carcinogenesis in Mice vol.13, pp.10, 2018, https://doi.org/10.3390/cancers13102292
  25. Central vs. Peripheral Action of Thyroid Hormone in Adaptive Thermogenesis: A Burning Topic vol.10, pp.6, 2021, https://doi.org/10.3390/cells10061327
  26. Droplet digital PCR or quantitative PCR for in-depth genomic and functional validation of genetically altered rodents vol.191, pp.None, 2018, https://doi.org/10.1016/j.ymeth.2021.04.001
  27. Inhibition of Cancer Cell Adhesion, Migration and Proliferation by a Bispecific Antibody that Targets two Distinct Epitopes on αv Integrins vol.433, pp.15, 2018, https://doi.org/10.1016/j.jmb.2021.167090
  28. Dual Mkk4 and Mkk7 Gene Deletion in Adult Mouse Causes an Impairment of Hippocampal Immature Granule Cells vol.22, pp.17, 2021, https://doi.org/10.3390/ijms22179545
  29. Should We Open Fire on Microglia? Depletion Models as Tools to Elucidate Microglial Role in Health and Alzheimer’s Disease vol.22, pp.18, 2018, https://doi.org/10.3390/ijms22189734
  30. Insights into Mechanisms of Tumorigenesis in Neuroendocrine Neoplasms vol.22, pp.19, 2018, https://doi.org/10.3390/ijms221910328
  31. Targeted deletion of PAC1 receptors in retinal neurons enhances neuron loss and axonopathy in a model of multiple sclerosis and optic neuritis vol.160, pp.None, 2018, https://doi.org/10.1016/j.nbd.2021.105524
  32. Interrogating lncRNA functions via CRISPR/Cas systems vol.18, pp.12, 2021, https://doi.org/10.1080/15476286.2021.1899500