Review
Free Access
Conditional alleles in mice: Practical considerations for tissue-specific knockouts
Kin-Ming Kwan,
Corresponding Author
Kin-Ming Kwan
Department of Molecular Genetics, University of Texas, M.D. Anderson Cancer Center, Houston, Texas
Department of Molecular Genetics, University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030Search for more papers by this authorKin-Ming Kwan,
Corresponding Author
Kin-Ming Kwan
Department of Molecular Genetics, University of Texas, M.D. Anderson Cancer Center, Houston, Texas
Department of Molecular Genetics, University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030Search for more papers by this author
LITERATURE CITED
- Abel ED, Kaulbach HC, Tian R, Hopkins JC, Duffy J, Doetschman T, Minnemann T, Boers ME, Hadro E, Oberste-Berghaus C, Quist W, Lowell BB, Ingwall JS, Kahn BB. 1999. Cardiac hypertrophy with preserved contractile function after selective deletion of GLUT4 from the heart. J Clin Invest 104: 1703–1714.
- Agah R, Frenkel PA, French BA, Michael LH, Overbeek PA, Schneider MD. 1997. Gene recombination in postmitotic cells. Targeted expression of Cre recombinase provokes cardiac-restricted, site-specific rearrangement in adult ventricular muscle in vivo. J Clin Invest 100: 169–179.
- Ahn K, Mishina Y, Hanks, MC, Behringer, RR, Crenshaw B III. 2001. BMPR-1A signaling is required for the formation of the apical ectodermal ridge and dorsal-ventral patterning of the limb. Development 128: 4449–4461.
- Ashery-Padan R, Marquardt T, Zhou X, Gruss P. 2000. Pax6 activity in the lens primordium is required for lens formation and for correct placement of a single retina in the eye. Genes Dev 14: 2701–2711.
- Backman SA, Stambolic V, Suzuki A, Haight J, Elia A, Pretorius J, Tsao MS, Shannon P, Bolon B, Ivy GO, Mak TW. 2001. Deletion of Pten in mouse brain causes seizures, ataxia and defects in soma size resembling Lhermitte-Duclos disease. Nat Genet 29: 396–403.
- Bates B, Rios M, Trumpp A, Chen C, Fan G, Bishop JM, Jaenisch R. 1999. Neurotrophin-3 is required for proper cerebellar development. Nat Neurosci 2: 115–117.
- Betz UA, Vosshenrich CA, Rajewsky K, Muller W. 1996. Bypass of lethality with mosaic mice generated by Cre-loxP-mediated recombination. Curr Biol 6: 1307–1316.
- Betz UA, Bloch W, < van den Broek M, Yoshida K, Taga T, Kishimoto T, Addicks K, Rajewsky K, Muller W. 1998. Postnatally induced inactivation of gp130 in mice results in neurological, cardiac, hematopoietic, immunological, hepatic, and pulmonary defects. J Exp Med 188: 1955–1965.
- Brakebusch C, Grose R, Quondamatteo F, Ramirez A, Jorcano JL, Pirro A, Svensson M, Herken R, Sasaki T, Timpl R, Werner S, Fassler R. 2000. Skin and hair follicle integrity is crucially dependent on beta 1 integrin expression on keratinocytes. EMBO J 19: 3990–4003.
- Brault V, Moore R, Kutsch S, Ishibashi M, Rowitch DH, McMahon AP, Sommer L, Boussadia O, Kemler R. 2001. Inactivation of the beta-catenin gene by Wnt1-Cre-mediated deletion results in dramatic brain malformation and failure of craniofacial development. Development 128: 1253–1264.
- Brocard J, Feil R, Chambon P, Metzger D. 1998. A chimeric Cre recombinase inducible by synthetic, but not by natural ligands of the glucocorticoid receptor. Nucl Acids Res 26: 4086–4090.
- Bruning JC, Michael MD, Winnay JN, Hayashi T, Horsch D, Accili D, Goodyear LJ, Kahn CR. 1998. A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol Cell 2: 559–569.
- Bruning JC, Gautam D, Burks DJ, Gillette J, Schubert M, Orban PC, Klein R, Krone W, Muller-Wieland D, Kahn CR. 2000. Role of brain insulin receptor in control of body weight and reproduction. Science 289: 2122–2125.
- Buchholz F, Angrand PO, Stewart AF. 1996. A simple assay to determine the functionality of Cre or FLP recombination targets in genomic manipulation constructs. Nucl Acids Res 24: 3118–3119.
- Buchholz F, Angrand PO, Stewart AF. 1998. Improved properties of FLP recombinase evolved by cycling mutagenesis. Nat Biotechnol 16: 657–662.
- Chang BH, Liao W, Li L, Nakamuta M, Mack D, Chan L. 1999. Liver-specific inactivation of the abetalipoproteinemia gene completely abrogates very low density lipoprotein/low density lipoprotein production in a viable conditional knockout mouse. J Biol Chem 274: 6051–6055.
- Chapman RS, Lourenco PC, Tonner E, Flint DJ, Selbert S, Takeda K, Akira S, Clarke AR, Watson CJ. 1999. Suppression of epithelial apoptosis and delayed mammary gland involution in mice with a conditional knockout of Stat3. Genes Dev 13: 2604–2616.
- Cheah SS, Behringer RR. Gene-targeting strategies. 2000. Methods Mol Biol 136: 455–463.
- Chen RZ, Akbarian S, Tudor M, Jaenisch R. 2001. Deficiency of methyl-CpG binding protein-2 in CNS neurons results in a Rett-like phenotype in mice. Nat Genet 27: 327–331.
- Clausen BE, Waldburger JM, Schwenk F, Barras E, Mach B, Rajewsky K, Forster I, Reith W. 1998. Residual MHC class II expression on mature dendritic cells and activated B cells in RFX5-deficient mice. Immunity 8: 143–155.
- Clausen BE, Burkhardt C, Reith W, Renkawitz R, Forster I. 1999. Conditional gene targeting in macrophages and granulocytes using LysMcre mice. Transgen Res 8: 265–277.
- Csankovszki G, Panning B, Bates B, Pehrson JR, Jaenisch R. 1999. Conditional deletion of Xist disrupts histone macroH2A localization but not maintenance of X inactivation. Nat Genet 22: 323–324.
- < de Alboran IM, O'Hagan RC, Gartner F, Malynn B, Davidson L, Rickert R, Rajewsky K, DePinho RA, Alt FW. 2001. Analysis of C-MYC function in normal cells via conditional gene-targeted mutation. Immunity 14: 45–55.
- DiSanto JP, Muller W, Guy-Grand D, Fischer A, Rajewsky K. 1995. Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor gamma chain. Proc Natl Acad Sci USA 92: 377–381.
- Dragatsis I, Levine MS, Zeitlin S. 2000. Inactivation of Hdh in the brain and testis results in progressive neurodegeneration and sterility in mice. Nat Genet 26: 300–306.
- Dymecki SM. 1996. Flp recombinase promotes site-specific DNA recombination in embryonic stem cells and transgenic mice. Proc Natl Acad Sci USA 93: 6191–6196.
- Dymecki SM. 2000. Gene targeting. AL Joyner, editor. Oxford: Oxford University Press. p 37.
- Fan G, Beard C, Chen RZ, Csankovszki G, Sun Y, Siniaia M, Biniszkiewicz D, Bates B, Lee PP, Kuhn R, Trumpp A, Poon C, Wilson CB, Jaenisch R. 2001. DNA hypomethylation perturbs the function and survival of CNS neurons in postnatal animals. J Neurosci 21: 788–797.
-
Farley FW,
Soriano P,
Steffen LS,
Dymecki SM.
2000.
Widespread recombinase expression using FLPeR (flipper) mice.
genesis
28:
106–110.
10.1002/1526-968X(200011/12)28:3/4<106::AID-GENE30>3.0.CO;2-T CAS PubMed Web of Science® Google Scholar
- Garratt AN, Voiculescu O, Topilko P, Charnay P, Birchmeier C. 2000. A dual role of erbB2 in myelination and in expansion of the Schwann cell precursor pool. J Cell Biol 148: 1035–1046.
- Gerber HP, Hillan KJ, Ryan AM, Kowalski J, Keller GA, Rangell L, Wright BD, Radtke F, Aguet M, Ferrara N. 1999. VEGF is required for growth and survival in neonatal mice. Development 126: 1149–1159.
- Giordano FJ, Gerber HP, Williams SP, VanBruggen N, Bunting S, Ruiz-Lozano P, Gu Y, Nath AK, Huang Y, Hickey R, Dalton N, Peterson KL, Ross J Jr, Chien KR, Ferrara N. 2001. A cardiac myocyte vascular endothelial growth factor paracrine pathway is required to maintain cardiac function. Proc Natl Acad Sci USA 98: 5780–5785.
- Giovannini M, Robanus-Maandag E, < van der Valk M, Niwa-Kawakita M, Abramowski V, Goutebroze L, Woodruff JM, Berns A, Thomas G. 2000. Conditional biallelic Nf2 mutation in the mouse promotes manifestations of human neurofibromatosis type 2. Genes Dev 14: 1617–1630.
- Groszer M, Erickson R, Scripture-Adams DD, Lesche R, Trumpp A, Zack JA, Kornblum HI, Liu X, Wu H. 2001. Negative regulation of neural stem/progenitor cell proliferation by the pten tumor suppressor gene in vivo. Science 294: 2186–2189.
- Gu H, Marth JD, Orban PC, Mossmann H, Rajewsky K. 1994. Deletion of a DNA polymerase beta gene segment in T cells using cell type-specific gene targeting. Science 265: 103–106.
- Haase VH, Glickman JN, Socolovsky M, Jaenisch R. 2001. Vascular tumors in livers with targeted inactivation of the von Hippel-Lindau tumor suppressor. Proc Natl Acad Sci USA 98: 1583–1588.
- Hajihosseini MK, Wilson S, < De Moerlooze L, Dickson C. 2001. A splicing switch and gain-of-function mutation in FgfR2-IIIc hemizygotes causes Apert/Pfeiffer-syndrome-like phenotypes. Proc Natl Acad Sci USA 98: 3855–3860.
- Harada N, Tamai Y, Ishikawa T, Sauer B, Takaku K, Oshima M, Taketo MM. 1999. Intestinal polyposis in mice with a dominant stable mutation of the beta-catenin gene. EMBO J 18: 5931–5942.
- Hayhurst GP, Lee YH, Lambert G, Ward JM, Gonzalez FJ. 2001. Hepatocyte nuclear factor 4alpha (nuclear receptor 2A1) is essential for maintenance of hepatic gene expression and lipid homeostasis. Mol Cell Biol 21: 1393–1403.
- He B, Deckelbaum RA, Miao D, Lipman ML, Pollak M, Goltzman D, Karaplis AC. 2001. Tissue-specific targeting of the pthrp gene: the generation of mice with floxed alleles. Endocrinology 142: 2070–2077.
- Hennet T, Hagen FK, Tabak LA, Marth JD. 1995. T-cell-specific deletion of a polypeptide N-acetylgalactosaminyl-transferase gene by site-directed recombination. Proc Natl Acad Sci USA 92: 12070–12074.
- Hirota H, Chen J, Betz UA, Rajewsky K, Gu Y, Ross J Jr, Muller W, Chien KR. 1999. Loss of a gp130 cardiac muscle cell survival pathway is a critical event in the onset of heart failure during biomechanical stress. Cell 97: 189–198.
- Horcher M, Souabni A, Busslinger M. 2001. Pax5/BSAP maintains the identity of B cells in late B lymphopoiesis. Immunity 14: 779–790.
- Huelsken J, Vogel R, Erdmann B, Cotsarelis G, Birchmeier W. 2001. beta-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin. Cell 105: 533–545.
- Huerta PT, Sun LD, Wilson MA, Tonegawa S. 2000. Formation of temporal memory requires NMDA receptors within CA1 pyramidal neurons. Neuron 25: 473–480.
- Imai T, Jiang M, Kastner P, Chambon P, Metzger D. 2001a. Selective ablation of retinoid X receptor alpha in hepatocytes impairs their lifespan and regenerative capacity. Proc Natl Acad Sci USA 98: 4581–4586.
- Imai T, Jiang M, Chambon P, Metzger D. 2001b. Impaired adipogenesis and lipolysis in the mouse upon selective ablation of the retinoid X receptor alpha mediated by atamoxifen-inducible chimeric Cre recombinase (Cre-ERT2) in adipocytes. Proc Natl Acad Sci USA 98: 224–228.
- Isermann B, Hendrickson SB, Zogg M, Wing M, Cummiskey M, Kisanuki YY, Yanagisawa M, Weiler H. 2001. Endothelium-specific loss of murine thrombomodulin disrupts the protein C anticoagulant pathway and causes juvenile-onset thrombosis. J Clin Invest 108: 537–546.
- Iwasato T, Datwani A, Wolf AM, Nishiyama H, Taguchi Y, Tonegawa S, Knopfel T, Erzurumlu RS, Itohara S. 2000. Cortex-restricted disruption of NMDAR1 impairs neuronal patterns in the barrel cortex. Nature 406: 726–731.
- Jackson-Grusby L, Beard C, Possemato R, Tudor M, Fambrough D, Csankovszki G, Dausman J, Lee P, Wilson C, Lander E, Jaenisch R. 2001. Loss of genomic methylation causes p53-dependent apoptosis and epigenetic deregulation. Nat Genet 27: 31–39.
- Jo D, Nashabi A, Doxsee C, Lin Q, Unutmaz D, Chen J, Ruley HE. 2001. Epigenetic regulation of gene structure and function with a cell-permeable Cre recombinase. Nat Biotechnol 19: 929–933.
- Jonkers J, Meuwissen R, < van Der Gulden H, Peterse H, < van Der Valk M, Berns A. 2001. Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer. Nat Genet 29: 418–425.
- Kaartinen V, Nagy A. 2001. Removal of the floxed neo gene from a conditional knockout allele by the adenoviral Cre recombinase in vivo. genesis 31: 126–129.
- Kellendonk C, Tronche F, Casanova E, Anlag K, Opherk C, Schutz G. 1999. Inducible site-specific recombination in the brain. J Mol Biol 285: 175–182.
- Kulkarni RN, Bruning JC, Winnay JN, Postic C, Magnuson MA, Kahn CR. 1999. Tissue-specific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in type 2 diabetes. Cell 96: 329–339.
- Kwon CH, Zhu X, Zhang J, Knoop LL, Tharp R, Smeyne RJ, Eberhart CG, Burger PC, Baker SJ. 2001. Pten regulates neuronal soma size: a mouse model of Lhermitte-Duclos disease. Nat Genet 29: 404–411.
- Lakso M, Sauer B, Mosinger B Jr, Lee EJ, Manning RW, Yu SH, Mulder KL, Westphal H. 1992. Targeted oncogene activation by site-specific recombination in transgenic mice. Proc Natl Acad Sci USA 89: 6232–6236.
- Lakso M, Pichel JG, Gorman JR, Sauer B, Okamoto Y, Lee E, Alt FW, Westphal H. 1996. Efficient in vivo manipulation of mouse genomic sequences at the zygote stage. Proc Natl Acad Sci USA 93: 5860–5865.
- Larsson NG, Wang J, Wilhelmsson H, Oldfors A, Rustin P, Lewandoski M, Barsh GS, Clayton DA. 1998. Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice. Nat Genet 18: 231–236.
- Lee YH, Sauer B, Johnson PF, Gonzalez FJ. 1997. Disruption of the c/ebp alpha gene in adult mouse liver. Mol Cell Biol 17: 6014–6022.
- 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. 2001. A critical role for dnmt1 and DNA methylation in T cell development, function, and survival. Immunity 15: 763–774.
- Leuker CE, Labow M, Muller W, Wagner N. 2001. Neonatally induced inactivation of the vascular cell adhesion molecule 1 gene impairs B cell localization and T cell-dependent humoral immune response. J Exp Med 193: 755–768.
- Lewandoski M, Sun X, Martin GR. 2000. Fgf8 signalling from the AER is essential for normal limb development. Nat Genet 26: 460–463.
- Li H, Wang J, Wilhelmsson H, Hansson A, Thoren P, Duffy J, Rustin P, Larsson NG. 2000a. Genetic modification of survival in tissue-specific knockout mice with mitochondrial cardiomyopathy. Proc Natl Acad Sci USA 97: 3467–4672.
- Li M, Indra AK, Warot X, Brocard J, Messaddeq N, Kato S, Metzger D, Chambon P. 2000b. Skin abnormalities generated by temporally controlled RXRalpha mutations in mouse epidermis. Nature 407: 633–636.
- Li M, Chiba H, Warot X, Messaddeq N, Gerard C, Chambon P, Metzger D. 2001. RXR-alpha ablation in skin keratinocytes results in alopecia and epidermal alterations. Development 128: 675–688.
- Liao Y, Day KH, Damon DN, Duling BR. 2001. Endothelial cell-specific knockout of connexin 43 causes hypotension and bradycardia in mice. Proc Natl Acad Sci USA 98: 9989–9994.
- Liu JL, Grinberg A, Westphal H, Sauer B, Accili D, Karas M, LeRoith D. 1998. Insulin-like growth factor-I affects perinatal lethality and postnatal development in a gene dosage-dependent manner: manipulation using the Cre/loxP system in transgenic mice. Mol Endocrinol 12: 1452–1462.
-
Lobe CG,
Nagy A.
1998.
Conditional genome alteration in mice.
BioEssays
20:
200–208.
10.1002/(SICI)1521-1878(199803)20:3<200::AID-BIES3>3.0.CO;2-V CAS PubMed Web of Science® Google Scholar
- Ludwig T, Fisher P, Murty V, Efstratiadis A. 2001. Development of mammary adenocarcinomas by tissue-specific knockout of Brca2 in mice. Oncogene 20: 3937–3948.
- Marquardt T, Ashery-Padan R, Andrejewski N, Scardigli R, Guillemot F, Gruss P. 2001. Pax6 is required for the multipotent state of retinal progenitor cells. Cell 105: 43–55.
- Marszalek JR, Liu X, Roberts EA, Chui D, Marth JD, Williams DS, Goldstein LS. 2000. Genetic evidence for selective transport of opsin and arrestin by kinesin-II in mammalian photoreceptors. Cell 102: 175–187.
- Matsuda M, Korn BS, Hammer RE, Moon YA, Komuro R, Horton JD, Goldstein JL, Brown MS, Shimomura I. 2001. SREBP cleavage-activating protein (SCAP) is required for increased lipid synthesis in liver induced by cholesterol deprivation and insulin elevation. Genes Dev 15: 1206–1216.
- Meuwissen R, Linn SC, < van der Valk M, Mooi WJ, Berns A. 2001. Mouse model for lung tumorigenesis through Cre/lox controlled sporadic activation of the K-Ras oncogene. Oncogene 20: 6551–6558.
- Meyers EN, Lewandoski M, Martin GR. 1998. An Fgf8 mutant allelic series generated by Cre- and Flp-mediated recombination. Nat Genet 18: 136–141.
- Minichiello L, Korte M, Wolfer D, Kuhn R, Unsicker K, Cestari V, Rossi-Arnaud C, Lipp HP, Bonhoeffer T, Klein R. 1999. Essential role for TrkB receptors in hippocampus-mediated learning. Neuron 24: 401–414.
- Moon AM, Capecchi MR. 2000. Fgf8 is required for outgrowth and patterning of the limbs. Nat Genet 26: 455–459.
- Moon AM, Boulet AM, Capecchi MR. 2000. Normal limb development in conditional mutants of Fgf4. Development 127: 989–996.
- Murakami Y, Kinoshita T, Maeda Y, Nakano T, Kosaka H, Takeda J. 1999. Different roles of glycosylphosphatidylinositol in various hematopoietic cells as revealed by a mouse model of paroxysmal nocturnal hemoglobinuria. Blood 94: 2963–2970.
-
Nagy A.
2000.
Cre recombinase: the universal reagent for genome tailoring.
genesis
26:
99–109.
10.1002/(SICI)1526-968X(200002)26:2<99::AID-GENE1>3.0.CO;2-B CAS PubMed Web of Science® Google Scholar
- Nagy A, Mar L. 2001. Creation and use of a Cre recombinase transgenic database. Meth Mol Biol 158: 95–106.
- Nagy A, Moens C, Ivanyi E, Pawling J, Gertsenstein M, Hadjantonakis AK, Pirity M, Rossant J. 1998. Dissecting the role of N-myc in development using a single targeting vector to generate a series of alleles. Curr Biol 8: 661–664.
- Norris DP, Robertson EJ. 1999. Asymmetric and node-specific nodal expression patterns are controlled by two distinct cis-acting regulatory elements. Genes Dev 13: 1575–1588.
- Nozaki M, Ohishi K, Yamada N, Kinoshita T, Nagy A, Takeda J. 1999. Developmental abnormalities of glycosylphosphatidylinositol-anchor-deficient embryos revealed by Cre/loxP system. Lab Invest 79: 293–299.
- O'Gorman S, Fox DT, Wahl GM. 1991. Recombinase-mediated gene activation and site-specific integration in mammalian cells. Science 251: 1351–1355.
- Orban PC, Chui D, Marth JD. 1992. Tissue- and site-specific DNA recombination in transgenic mice. Proc Natl Acad Sci USA 89: 6861–6865.
- Postic C, Shiota M, Niswender KD, Jetton TL, Chen Y, Moates JM, Shelton KD, Lindner J, Cherrington AD, Magnuson MA. 1999. Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic beta cell-specific gene knockouts using Cre recombinase. J Biol Chem 274: 305–315.
- Puccio H, Simon D, Cossee M, Criqui-Filipe P, Tiziano F, Melki J, Hindelang C, Matyas R, Rustin P, Koenig M. 2001. Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits. Nat Genet 27: 181–186.
- Raabe M, Veniant MM, Sullivan MA, Zlot CH, Bjorkegren J, Nielsen LB, Wong JS, Hamilton RL, Young SG. 1999. Analysis of the role of microsomal triglyceride transfer protein in the liver of tissue-specific knockout mice. J Clin Invest 103: 1287–1298.
- Radtke F, Wilson A, Stark G, Bauer M, < van Meerwijk J, MacDonald HR, Aguet M. 1999. Deficient T cell fate specification in mice with an induced inactivation of Notch1. Immunity 10: 547–558.
- Raghavan S, Bauer C, Mundschau G, Li Q, Fuchs E. 2000. Conditional ablation of beta1 integrin in skin. Severe defects in epidermal proliferation, basement membrane formation, and hair follicle invagination. J Cell Biol 150: 1149–1160.
- Rios M, Fan G, Fekete C, Kelly J, Bates B, Kuehn R, Lechan RM, Jaenisch R. 2001. Conditional deletion of brain-derived neurotrophic factor in the postnatal brain leads to obesity and hyperactivity. Mol Endocrinol 15: 1748–1757.
- Rodriguez CI, Buchholz F, Galloway J, Sequerra R, Kasper J, Ayala R, Stewart AF, Dymecki SM. 2000. High-efficiency deleter mice show that FLPe is an alternative to Cre-loxP. Nat Genet 25: 139–140.
- Rohlmann A, Gotthardt M, Willnow TE, Hammer RE, Herz J. 1996. Sustained somatic gene inactivation by viral transfer of Cre recombinase. Nat Biotechnol 14: 1562–1565.
- Rohlmann A, Gotthardt M, Hammer RE, Herz J. 1998. Inducible inactivation of hepatic LRP gene by cre-mediated recombination confirms role of LRP in clearance of chylomicron remnants. J Clin Invest 101: 689–695.
- Rucker EB, Dierisseau P, Wagner KU, Garrett L, Wynshaw-Boris A, Flaws JA, Hennighausen L. 2000. Bcl-x and Bax regulate mouse primordial germ cell survival and apoptosis during embryogenesis. Mol Endocrinol 14: 1038–1052.
- Sakai T, Johnson KJ, Murozono M, Sakai K, Magnuson MA, Wieloch T, Cronberg T, Isshiki A, Erickson HP, Fassler R. 2001. Plasma fibronectin supports neuronal survival and reduces brain injury following transient focal cerebral ischemia but is not essential for skin-wound healing and hemostasis. Nat Med 7: 324–330.
- Sano S, Itami S, Takeda K, Tarutani M, Yamaguchi Y, Miura H, Yoshikawa K, Akira S, Takeda J. 1999. Keratinocyte-specific ablation of Stat3 exhibits impaired skin remodeling, but does not affect skin morphogenesis. EMBO J 18: 4657–4668.
- Sauer B, Henderson N. 1988. Site-specific DNA recombination in mammalian cells by the Cre recombinase of bacteriophage P1. Proc Natl Acad Sci USA 85: 5166–5170.
- Schaft J, Ashery-Padan R, < van Der Hoeven F, Gruss P, Stewart AF. 2001. Efficient FLP recombination in mouse ES cells and oocytes. genesis 31: 6–10.
- Schwenk F, Kuhn R, Angrand PO, Rajewsky K, Stewart AF. 1998. Temporally and spatially regulated somatic mutagenesis in mice. Nucl Acids Res 26: 1427–1432.
- Shibata H, Toyama K, Shioya H, Ito M, Hirota M, Hasegawa S, Matsumoto H, Takano H, Akiyama T, Toyoshima K, Kanamaru R, Kanegae Y, Saito I, Nakamura Y, Shiba K, Noda T. 1997. Rapid colorectal adenoma formation initiated by conditional targeting of the Apc gene. Science 278: 120–123.
- Silva JP, Kohler M, Graff C, Oldfors A, Magnuson MA, Berggren PO, Larsson NG. 2000. Impaired insulin secretion and beta-cell loss in tissue-specific knockout mice with mitochondrial diabetes. Nat Genet 26: 336–340.
- Sjogren K, Liu JL, Blad K, Skrtic S, Vidal O, Wallenius V, LeRoith D, Tornell J, Isaksson OG, Jansson JO, Ohlsson C. 1999. Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice. Proc Natl Acad Sci USA 96: 7088–7092.
- Stark WM, Boocock MR, Sherratt DJ. 1992. Catalysis by site-specific recombinases. Trends Genet 8: 432–439.
- Sun X, Lewandoski M, Meyers EN, Liu YH, Maxson RE Jr, Martin GR. 2000. Conditional inactivation of Fgf4 reveals complexity of signalling during limb bud development. Nat Genet 25: 83–86.
- Sund NJ, Ang SL, Sackett SD, Shen W, Daigle N, Magnuson MA, Kaestner KH. 2000. Hepatocyte nuclear factor 3beta (Foxa2) is dispensable for maintaining the differentiated state of the adult hepatocyte. Mol Cell Biol 20: 5175–5183.
- Sund NJ, Vatamaniuk MZ, Casey M, Ang SL, Magnuson MA, Stoffers DA, Matschinsky FM, Kaestner KH. 2001. Tissue-specific deletion of Foxa2 in pancreatic beta cells results in hyperinsulinemic hypoglycemia. Genes Dev 15: 1706–1715.
- Suzuki A, Yamaguchi MT, Ohteki T, Sasaki T, Kaisho T, Kimura Y, Yoshida R, Wakeham A, Higuchi T, Fukumoto M, Tsubata T, Ohashi PS, Koyasu S, Penninger JM, Nakano T, Mak TW. 2001. T cell-specific loss of Pten leads to defects in central and peripheral tolerance. Immunity 14: 523–534.
-
Takahama Y,
Ohishi K,
Tokoro Y,
Sugawara T,
Yoshimura Y,
Okabe M,
Kinoshita T,
Takeda J.
1998.
Functional competence of T cells in the absence of glycosylphosphatidylinositol-anchored proteins caused by T cell-specific disruption of the Pig-a gene.
Eur J Immunol
28:
2159–2166.
10.1002/(SICI)1521-4141(199807)28:07<2159::AID-IMMU2159>3.0.CO;2-B CAS PubMed Web of Science® Google Scholar
- Takeda K, Kaisho T, Yoshida N, Takeda J, Kishimoto T, Akira S. 1998. Stat3 activation is responsible for IL-6-dependent T cell proliferation through preventing apoptosis: generation and characterization of T cell-specific Stat3-deficient mice. J Immunol 161: 4652–4660.
- Takeda K, Clausen BE, Kaisho T, Tsujimura T, Terada N, Forster I, Akira S. 1999. Enhanced Th1 activity and development of chronic enterocolitis in mice devoid of Stat3 in macrophages and neutrophils. Immunity 10: 39–49.
- Tarutani M, Itami S, Okabe M, Ikawa M, Tezuka T, Yoshikawa K, Kinoshita T, Takeda J. 1997. Tissue-specific knockout of the mouse Pig-a gene reveals important roles for GPI-anchored proteins in skin development. Proc Natl Acad Sci USA 94: 7400–7405.
- Terauchi Y, Sakura H, Yasuda K, Iwamoto K, Takahashi N, Ito K, Kasai H, Suzuki H, Ueda O, Kamada N, et al. 1995. Pancreatic beta-cell-specific targeted disruption of glucokinase gene. Diabetes mellitus due to defective insulin secretion to glucose. J Biol Chem 270: 30253–30256.
- Tomita S, Sinal CJ, Yim SH, Gonzalez FJ. 2000. Conditional disruption of the aryl hydrocarbon receptor nuclear translocator (Arnt) gene leads to loss of target gene induction by the aryl hydrocarbon receptor and hypoxia-inducible factor 1alpha. Mol Endocrinol 14: 1674–1681.
- Torres RM, Kuhn R. 1997. Laboratory protocols for conditional gene targeting. RM Torres, R Kuhn, editors. Oxford: Oxford University Press. p 167.
- Tronche F, Kellendonk C, Kretz O, Gass P, Anlag K, Orban PC, Bock R, Klein R, Schutz G. 1999. Disruption of the glucocorticoid receptor gene in the nervous system results in reduced anxiety. Nat Genet 23: 99–103.
- Volarevic S, Stewart MJ, Ledermann B, Zilberman F, Terracciano L, Montini E, Grompe M, Kozma SC, Thomas G. 2000. Proliferation, but not growth, blocked by conditional deletion of 40S ribosomal protein S6. Science 288: 2045–2047.
- Vooijs M, van der Valk M, te Riele H, Berns A. 1998. Flp-mediated tissue-specific inactivation of the retinoblastoma tumor suppressor gene in the mouse. Oncogene 17: 1–12.
- Wagner KU, Claudio E, Rucker EB 3rd, Riedlinger G, Broussard C, Schwartzberg PL, Siebenlist U, Hennighausen L. 2000. Conditional deletion of the Bcl-x gene from erythroid cells results in hemolytic anemia and profound splenomegaly. Development 127: 4949– 4958.
- Waltz SE, Eaton L, Toney-Earley K, Hess KA, Peace BE, Ihlendorf JR, Wang MH, Kaestner KH, Degen SJ. 2001. Ron-mediated cytoplasmic signaling is dispensable for viability but is required to limit inflammatory responses. J Clin Invest 108: 567–76.
- Wang Y, Krushel LA, Edelman GM. 1996. Targeted DNA recombination in vivo using an adenovirus carrying the cre recombinase gene. Proc Natl Acad Sci USA 93: 3932–3936.
- Wang J, Wilhelmsson H, Graff C, Li H, Oldfors A, Rustin P, Bruning JC, Kahn CR, Clayton DA, Barsh GS, Thoren P, Larsson NG. 1999. Dilated cardiomyopathy and atrioventricular conduction blocks induced by heart-specific inactivation of mitochondrial DNA gene expression. Nat Genet 21: 133–137.
- Wolfer A, Bakker T, Wilson A, Nicolas M, Ioannidis V, Littman DR, Wilson CB, Held W, MacDonald HR, Radtke F. 2001. Inactivation of Notch 1 in immature thymocytes does not perturb CD4 or CD8T cell development. Nat Immunol 2: 235–241.
- Xiao Y, Weaver DT. 1997. Conditional gene targeted deletion by Cre recombinase demonstrates the requirement for the double-strand break repair Mre11 protein in murine embryonic stem cells. Nucl Acids Res 25: 2985–2991.
- Xu X, Wagner KU, Larson D, Weaver Z, Li C, Ried T, Hennighausen L, Wynshaw-Boris A, Deng CX. 1999. Conditional mutation of Brca1 in mammary epithelial cells results in blunted ductal morphogenesis and tumour formation. Nat Genet 22: 37–43
- Xu X, Li C, Garrett-Beal L, Larson D, Wynshaw-Boris A, Deng CX. 2001. Direct removal in the mouse of a floxed neo gene from a three-loxP conditional knockout allele by two novel approaches. genesis 30: 1–6.
- Yakar S, Liu JL, Stannard B, Butler A, Accili D, Sauer B, LeRoith D. 1999. Normal growth and development in the absence of hepatic insulin-like growth factor I. Proc Natl Acad Sci USA 96: 7324–7329.
- Yu Y, Bradley A. 2001. Mouse genomic technologies engineering chromosomal rearrangements in mice. Nat Rev Genet 2: 780–790.
- Zhao L, Bakke M, Parker KL. 2001a. Pituitary-specific knockout of steroidogenic factor 1. Mol Cell Endocrinol 185: 27–32.
- Zhao L, Bakke M, Krimkevich Y, Cushman LJ, Parlow AF, Camper SA, Parker KL. 2001b. Hypomorphic phenotype in mice with pituitary-specific knockout of steroidogenic factor 1. genesis 30: 65–69.
- Zhu Y, Romero MI, Ghosh P, Ye Z, Charnay P, Rushing EJ, Marth JD, Parada LF. 2001. Ablation of NF1 function in neurons induces abnormal development of cerebral cortex and reactive gliosis in the brain. Genes Dev 15: 859–876.
- Zisman A, Peroni OD, Abel ED, Michael MD, Mauvais-Jarvis F, Lowell BB, Wojtaszewski JF, Hirshman MF, Virkamaki A, Goodyear LJ, Kahn CR, Kahn BB. 2000. Targeted disruption of the glucose transporter 4 selectively in muscle causes insulin resistance and glucose intolerance. Nat Med 6: 924–928.
Citing Literature
