心肌病

干细胞打靶，Gata4外显子3上游和外显子5下游各有一个loxP位点。

Watt AJ; Battle MA; Li J; Duncan SA. 2004. GATA4 is essential for formation of the proepicardium and regulates cardiogenesis. Proc Natl Acad Sci U S A 101(34):12573-8.

cre工具小鼠

转基因小鼠

cre报告鼠

该靶向载体由CMV增强子/鸡β -肌动蛋白核心启动子(pCA)驱动loxp侧边、n端膜标记、优化的DsRed荧光蛋白变体(称为串联二聚体番茄或td番茄)序列的表达，然后是聚腺苷酸化信号。紧挨着第二个loxP位点的远端是一个n端膜标记的增强型绿色荧光蛋白(EGFP)序列本身，随后是一个聚腺苷酸化信号。在表达载体的远端也有一个前端侧的neo盒。

1Muzumdar MD; Tasic B; Miyamichi K; Li L; Luo L. 2007. A global double-fluorescent Cre reporter mouse. Genesis 45(9):593-605. [PubMed: 17868096]  [MGI Ref ID J:124702] 2Ahrens MJ; Romereim S; Dudley AT. 2011. A re-evaluation of two key reagents for in vivo studies of Wnt signaling. Dev Dyn :. [PubMed: 21793100]  [MGI Ref ID J:174609]

工具小鼠

将含有剪接受体位点的增强flp盒连接到下游的PGK-neo盒上，插入内源性基因座。据报道，在携带报告基因的转基因小鼠中，有效的frt特异性重组反应了Gt(ROSA)26Sor在植入前的组成性表达，通过将FLPe盒插入ROSA26敲入载体构建了一个敲入结构(R26Fki)。该结构包括一个由小鼠磷酸甘油酸激酶启动子驱动的新霉素抗性基因。该构建体被电孔到129S4/ s4jaesor来源的AK7胚胎干细胞(ES)中，从而扰乱Gt(ROSA)26Sor位点。利用正确定位的ES细胞生成嵌合体。

1Farley FW; Soriano P; Steffen LS; Dymecki SM. 2000. Widespread recombinase expression using FLPeR (Flipper) mice Genesis 28(3-4):106-10. [PubMed: 11105051]  [MGI Ref ID J:66893] 2Affar el B; Gay F; Shi Y; Liu H; Huarte M; Wu S; Collins T; Li E; Shi Y. 2006. Essential dosage-dependent functions of the transcription factor yin yang 1 in late embryonic development and cell cycle progression. Mol Cell Biol 26(9):3565-81. [PubMed: 16611997]  [MGI Ref ID J:108369]

工具小鼠

该小鼠是敲入两种基因元件R26-rtTA和Col1a1：：tetO-4F2A，表达rtTA-M2蛋白，4F2A盒包含四个小鼠重编程基因Oct4（Pou5f1； POU域，第5类，转录因子1），Sox2（包含基因2的SRY-box），Klf4（类似Kruppel的因子4（肠））和c-Myc （Myc；骨髓细胞瘤癌基因）

1Carey BW; Markoulaki S; Beard C; Hanna J; Jaenisch R. 2010. Single-gene transgenic mouse strains for reprogramming adult somatic cells. Nat Methods 7(1):56-9. [PubMed: 20010831]  [MGI Ref ID J:157298]  2Hochedlinger K; Yamada Y; Beard C; Jaenisch R. 2005. Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues. Cell 121(3):465-77. [PubMed: 15882627]  [MGI Ref ID J:98920] 

cre工具小鼠

转基因小鼠 

1Hennet 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 U S A 92(26):12070-4. [PubMed: 8618846]  [MGI Ref ID J:67674] 2Garvin AM; Pawar S; Marth JD; Perlmutter RM. 1988. Structure of the murine lck gene and its rearrangement in a murine lymphoma cell line. Mol Cell Biol 8(8):3058-64. [PubMed: 2850479]  [MGI Ref ID J:9539]

cre工具鼠

将含有完整Foxp3基因的188kb C57BL/6J小鼠细菌人工染色体RP23-143D8插入增强绿色荧光蛋白(EGFP)，融合到密码子优化的“人源化”cre重组酶中进行修饰，显微注射NOD/ShiLtJ受精卵，获得转基因小鼠。

1. Zhou X; Jeker LT; Fife BT; Zhu S; Anderson MS; McManus MT; Bluestone JA. 2008. Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity. J Exp Med 205(9):1983-91. [PubMed: Bluestone J. 2010. A low expressing line derived from the same founder as the previously reported Tg(Foxp3-EGFP/cre)1aJbs high expressing transgene line MGI Direct Data Submission :.  [MGI Ref ID J:157603] 2. Lee AJ; Wu X; Cheng H; Zhou X; Cheng X; Sun SC. 2010. CARMA1 regulation of regulatory T cell development involves modulation of interleukin-2 receptor signaling. J Biol Chem 285(21):15696-703. [PubMed: 20233721]  [MGI Ref ID J:163899]

cre报告工具鼠

转基因小鼠

1 Soriano P. 1999. Generalized lacZ expression with the ROSA26 Cre reporter strain [letter] Nat Genet 21(1):70-1. [PubMed: 9916792]  [MGI Ref ID J:64292] 2 Andl T; Ahn K; Kairo A; Chu EY; Wine-Lee L; Reddy ST; Croft NJ; Cebra-Thomas JA; Metzger D; Chambon P; Lyons KM; Mishina Y; Seykora JT; Crenshaw EB 3rd; Millar SE. 2004. Epithelial Bmpr1a regulates differentiation and proliferation in postnatal hair follicles and is essential for tooth development. Development 131(10):2257-68. [PubMed: 15102710]  [MGI Ref ID J:91054]

cre工具小鼠

转基因小鼠

1 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. 2008. Notch2 integrates signaling by the transcription factors RBP-J and CREB1 to promote T cell cytotoxicity. Nat Immunol 9(10):1140-7. [PubMed: 18724371] [MGI Ref ID J:141009] 2 Sugimoto K; Maekawa Y; Kitamura A; Nishida J; Koyanagi A; Yagita H; Kojima H; Chiba S; Shimada M; Yasutomo K. 2010. Notch2 signaling is required for potent antitumor immunity in vivo. J Immunol 184(9):4673-8. [PubMed: 20351182] [MGI Ref ID J:160468]

cre工具小鼠

转基因小鼠 

1 Stranges PB; Watson J; Cooper CJ; Choisy-Rossi CM; Stonebraker AC; Beighton RA; Hartig H; Sundberg JP; Servick S; Kaufmann G; Fink PJ; Chervonsky AV. 2007. Elimination of antigen-presenting cells and autoreactive T cells by Fas contributes to prevention of autoimmunity. Immunity 26(5):629-41. [PubMed: 17509906] [MGI Ref ID J:123556] 2Brocker T; Riedinger M; Karjalainen K. 1997. Targeted expression of major histocompatibility complex (MHC) class II molecules demonstrates that dendritic cells can induce negative but not positive selection of thymocytes in vivo. J Exp Med 185(3):541-50. [PubMed: 9053454] [MGI Ref ID J:38890]

癫痫性脑病。

利用Crispr/cas9技术制备Cplx1敲除大鼠

Wolfram综合征

利用Crispr/cas9技术制备Wfs1敲除大鼠