癌症

在ctnna1基因外显子2的两端插入loxp位点

Vasioukhin V; Bauer C; Degenstein L; Wise B; Fuchs E. 2001. Hyperproliferation and defects in epithelial polarity upon conditional ablation of alpha-catenin in skin. Cell 104(4):605-17PubMed: 11239416MGI: J:67797

肿瘤疾病相关模型小鼠

基因打靶

1. Carver LA,Schnitzer JE.Caveolae:mining little caves for new cancer targets[J].Nat Rev Cancer,2003,3 (8):571-81. 2. Capozza F,Williams TM,Schubert W,et al.Absence of caveolin-1 sensitizes mouse skin to carcinogen-induced epidermalhyperplasia and tumor formation[J].Am J Pathol,2003,162 (6):2029-39. 3. Williams TM,Cheung MW,Park DS,et al.Loss of caveolin-1 gene expression accelerates the development of dysplastic mammary lesions in tumor-prone transgenic mice[J].Mol Biol Cell,2003,14(3):1027-42. 4. Lin SY,Yeh KT,Chen WT,et al.Promoter CpG methylation of caveolin-1 in sporadic colorectal cancer[J].Anticancer Res,2004,24(3a):1645-50. 5. ]Han SE,Park KH,Lee G,et al.Mutation and aberrant expression of Caveolin-1 in human oral squamous cell carcinomas and oral cancer cell lines[J].Int J Oncol,2004,24(2):435-40.

肿瘤疾病相关模型小鼠

基因打靶

1 Allen DM, van Praag H, Ray J, et al. Ataxia telangiectasia mutated is essential during adult neurogenesis. Genes Dev. 15: 554-566, 2001. 2 Bakkenist CJ, Kastan MB. DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421: 499-506, 2003. 3 Banin S, Moyal L, Shieh SY, et al. Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science 281: 1674-1677, 1998. 4 Bao S, Tibbetts RS, Brumbaugh KM, et al. ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses. Nature 411: 969-974, 2001. 5 Bartkova J, Horejsi Z, Koed K, et al. DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 434: 864-870, 2005. 6 Bartkova J, Rezaei N, Liontos M. Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature 444: 633-637, 2006 7 Falck J, Coates J, Jackson SP. Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature 434: 605-611, 2005. 8 Falck J, Petrini JHJ, Williams B, et al. The DNA damage-dependent intra-S phase checkpoint is regulated by parallel pathways. Nature Genet. 30: 290-294, 2002.

肿瘤疾病相关模型小鼠

基因打靶

1. Bergamaschi D., Samuels Y., O’Neil N.J., Trigiante G., Crook T., Hsieh J.K., O’Connor D.J., Zhong S., Campargue I., Tomlinson M.L. et al. 2003. iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human. Nat. Genet. 33: 162167. 2. Bergamaschi D., Samuels Y., Jin B., Duraisingham S., Crook T., Lu X. 2004. ASPP1 and ASPP2: Common activators of p53 family members. Mol. Cell. Biol. 24: 13411350. 3. Chen Y., Liu W., Naumovski L., Neve R.L. 2003. ASPP2 inhibits APP-BP1-mediated NEDD8 conjugation to cullin-1 and decreases APP-BP1-induced cell proliferation and neuronal apoptosis. J. Neurochem. 85: 801809.

神经疾病相关

基因打靶

1 Baek SH, Ohgi KA, Rose DW,et al. Exchange of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-kappa-B and beta-amyloid precursor protein. Cell 110: 55-67, 2002. 2 Blanco G, Irving NG, Brown SD, et al.Mapping of the human and murine X11-like genes (APBA2 and Apba2), the murine Fe65 gene (Apbb1), and the human Fe65-like gene (APBB2): genes encoding phosphotyrosine-binding domain proteins that interact with the Alzheimer's disease amyloid precursor protein. Mammalian Genome 9: 473-475, 1998. 3 Bressler SL, Gray MD, Sopher BL,et al. cDNA cloning and chromosome mapping of the human Fe65 gene: interaction of the conserved cytoplasmic domains of the human beta-amyloid precursor protein and its homologues with the mouse Fe65 protein. Hum. Molec. Genet. 5: 1589-1598, 1996. 4 Cao X, Sudhof TC. A transcriptionally active complex of APP with Fe65 and histone acetyltransferase Tip60. Science 293: 115-120, 2001. Note: Erratum: Science 293: 1437 only, 2001.

骨骼肌和心肌特异性cre工具小鼠

转基因

结肠上皮cre工具小鼠

转基因

1Hinoi T; Akyol A; Theisen BK; Ferguson DO; Greenson JK; Williams BO; Cho KR; Fearon ER. 2007. Mouse model of colonic adenoma-carcinoma progression based on somatic Apc inactivation. Cancer Res 67(20):9721-30. [PubMed: 17942902] [MGI Ref ID J:126018] 2Feng Y; Bommer GT; Zhai Y; Akyol A; Hinoi T; Winer I; Lin HV; Cadigan KM; Cho KR; Fearon ER. 2007. Drosophila split ends homologue SHARP functions as a positive regulator of Wnt/beta-catenin/T-cell factor signaling in neoplastic transformation. Cancer Res 67(2):482-91. [PubMed: 17234755] [MGI Ref ID J:117412] 3Miller SJ; Joshi BP; Feng Y; Gaustad A; Fearon ER; Wang TD. 2011. In vivo fluorescence-based endoscopic detection of colon dysplasia in the mouse using a novel peptide probe. PLoS One 6(3):e17384. [PubMed: 21408169] [MGI Ref ID J:171709]

血管内皮细胞特异性cre工具小鼠

转基因

1.Alva JA; Zovein AC; Monvoisin A; Murphy T; Salazar A; Harvey NL; Carmeliet P; Iruela-Arispe ML. 2006. VE-Cadherin-Cre-recombinase transgenic mouse: A tool for lineage analysis and gene deletion in endothelial cells. Dev Dyn 235(3):759-67. [PubMed: 16450386] [MGI Ref ID J:106155] 2.Corada M; Nyqvist D; Orsenigo F; Caprini A; Giampietro C; Taketo MM; Iruela-Arispe ML; Adams RH; Dejana E. 2010. The Wnt/beta-catenin pathway modulates vascular remodeling and specification by upregulating Dll4/Notch signaling. Dev Cell 18(6):938-49. [PubMed: 20627076] [MGI Ref ID J:163848] 3.Economopoulou M; Langer HF; Celeste A; Orlova VV; Choi EY; Ma M; Vassilopoulos A; Callen E; Deng C; Bassing CH; Boehm M; Nussenzweig A; Chavakis T. 2009. Histone H2AX is integral to hypoxia-driven neovascularization. Nat Med 15(5):553-8. [PubMed: 19377486] [MGI Ref ID J:149487] 4.Genetic Resource Sciences at The Jackson Laboratory. 2012. Expression/Specificity Patterns of Cre Alleles, 2011 MGI Direct Data Submission :. [MGI Ref ID J:184578] Genetic Resource Sciences at The Jackson Laboratory. 2008. Expression/Specificity patterns of Cre transgenes MGI Direct Data Submission :. [MGI Ref ID J:137887]

肌肉组织特异cre工具小鼠

转基因

1.Miniou P; Tiziano D; Frugier T; Roblot N; Le Meur M; Melki J. 1999. Gene targeting restricted to mouse striated muscle lineage. Nucleic Acids Res 27(19):e27. [PubMed: 10481039] [MGI Ref ID J:67906] 2.Agrawal PB; Joshi M; Savic T; Chen Z; Beggs AH. 2012. Normal myofibrillar development followed by progressive sarcomeric disruption with actin accumulations in a mouse Cfl2 knockout demonstrates requirement of cofilin-2 for muscle maintenance. Hum Mol Genet :. [PubMed: 22343409] [MGI Ref ID J:182571] 3.Buj-Bello A; Laugel V; Messaddeq N; Zahreddine H; Laporte J; Pellissier JF; Mandel JL. 2002. The lipid phosphatase myotubularin is essential for skeletal muscle maintenance but not for myogenesis in mice. Proc Natl Acad Sci U S A 99(23):15060-5. [PubMed: 12391329] [MGI Ref ID J:81791] Chambon C; Duteil D; Vignaud A; Ferry A; Messaddeq N; Malivindi R; Kato S; Chambon P; Metzger D. 2010. Myocytic androgen receptor controls the strength but not the mass of limb muscles. Proc Natl Acad Sci U S A 107(32):14327-32. [PubMed: 20660752] [MGI Ref ID J:163603] 4.Charvet C; Houbron C; Parlakian A; Giordani J; Lahoute C; Bertrand A; Sotiropoulos A; Renou L; Schmitt A; Melki J; Li Z; Daegelen D; Tuil D. 2006. New role for serum response factor in postnatal skeletal muscle growth and regeneration via the interleukin 4 and insulin-like growth factor 1 pathways. Mol Cell Biol 26(17):6664-74. [PubMed: 16914747] [MGI Ref ID J:112113]

这些转基因小鼠在大鼠nestin启动子和增强子的调控下表达Cre重组酶。转基因插入物的半合子小鼠是可存活的，可生育的，大小正常，没有任何明显的生理或行为异常。利用携带β-半乳糖苷酶转基因（其表达依赖于Cre介导的重组）的报告菌株进行的初步研究表明，Cre主要在中枢和外周神经系统表达，少数分离的肾脏和心脏细胞也表达活性。供体研究者指出，Cre重组酶活性在胚胎第11天出现在神经组织中。转基因插入位置在12号染色体上，由FISH分析确定。将含有人类生长激素多聚腺苷酸化信号和Cre重组酶基因的转基因构建体注射到B6SJLF2卵母细胞中，该重组酶基因受启动子和存在于大鼠巢蛋白基因第二内含子中的神经系统特异性增强子的控制。将创始动物培育成野生型C57BL/6J小鼠。经FISH分析，转基因插入位点位于12号染色体上。

靶基因符号：Nes11Cre; NesCre; Tg(Nes-cre); n-Cre+; nestin-Cre; nestin/Cre; 构建信息： 该基因在大鼠巢蛋白启动子的控制下表达Cre重组酶。该启动子在神经元和胶质细胞前体表达Cre重组酶。胚胎第11天，神经组织中存在Cre重组酶活性。[MGI参考ID J:13340][MGI参考ID J:164338][MGI参考ID J:57315]

1Tronche 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(1):99-103. 2Bruning 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 [see comments] Science 289(5487):2122-5. 3Delacour A; Nepote V; Trumpp A; Herrera PL. 2004. Nestin expression in pancreatic exocrine cell lineages. Mech Dev 121(1):3-14. 4Gao Q; Wolfgang MJ; Neschen S; Morino K; Horvath TL; Shulman GI; Fu XY. 2004. Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation. Proc Natl Acad Sci U S A 101(13):4661-6. 5Graus-Porta D; Blaess S; Senften M; Littlewood-Evans A; Damsky C; Huang Z; Orban P; Klein R; Schittny JC; Muller U. 2001. Beta1-class integrins regulate the development of laminae and folia in the cerebral and cerebellar cortex. Neuron 31(3):367-79. 6Haigh JJ; Morelli PI; Gerhardt H; Haigh K; Tsien J; Damert A; Miquerol L; Muhlner U; Klein R; Ferrara N; Wagner EF; Betsholtz C; Nagy A. 2003. Cortical and retinal defects caused by dosage-dependent reductions in VEGF-A paracrine signaling. Dev Biol 262(2):225-41.

平滑肌和心肌细胞特异cre工具小鼠

干细胞打靶

1Zhang J; Zhong W; Cui T; Yang M; Hu X; Xu K; Xie C; Xue C; Gibbons GH; Liu C; Li L; Chen YE. 2006. Generation of an adult smooth muscle cell-targeted Cre recombinase mouse model. Arterioscler Thromb Vasc Biol 26(3):e23-4. [PubMed: 16484601] [MGI Ref ID J:119865] 2Chang L; Villacorta L; Zhang J; Garcia-Barrio MT; Yang K; Hamblin M; Whitesall SE; D'Alecy LG; Chen YE. 2009. Vascular smooth muscle cell-selective peroxisome proliferator-activated receptor-gamma deletion leads to hypotension. Circulation 119(16):2161-9. [PubMed: 19364979] 3Hamblin M; Chang L; Zhang H; Yang K; Zhang J; Chen YE. 2011. Vascular smooth muscle cell peroxisome proliferator-activated receptor-gamma mediates pioglitazone-reduced vascular lesion formation. Arterioscler Thromb Vasc Biol 31(2):352-9. [PubMed: 21088248] [MGI Ref ID J:184182]

免疫相关动物模型

靶基因信息：TCR, human 构建信息： 表达位点：全身表达