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品系编号 T001492
品系名称 NOD-Prkdcem26Cd52/Nju
曾用名
品系简称 NOD SCID/Nju
品系来源
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购买 在线订购
入库时间 2014-08-15
相关基因 prkdc
品系类型 Knock outCas 9
背景 [N000235] NOD/ShiLtJNju
对照鼠 同窝阴性
提供基因型 (prkdc)KO/KO;(prkdc)KO/wt
毛色 白色
引入代数
当前代数
繁育方式
保存方式 活体冷冻
平均单胎产仔量 0
建议繁殖笼淘汰周期 8 months
母性 正常
品系描述

PRKDC(protein kinase, DNA-activated, catalytic polypeptide),别名HYRC,p350,DNAPK, DNPK1, HYRC1, IMD26, XRCC7, DNA-PKcs,属于PI3/PI4-激酶家族,主要编码DNA依赖性蛋白激酶(DNA-PK)的催化亚基。PRKDC蛋白在结合两个小的调节亚基(Ku70和Ku80)后形成DNA-PK,而DNA-PK能够对断裂的双链DNA进行修复和损伤应答[1]。 PRKDC蛋白可维持端粒的稳定性,参与免疫蛋白质的位置特异性V(D)J重组反应[2]和逆转录病毒DNA的整合[3]。此外,PRKDC蛋白对c-myc蛋白稳定性起到调控作用,从而在一定程度上参与细胞的恶性转化过程[4]。 NBRI利用CRISPR/Cas9技术和囊胚注射技术,在PRKDC基因部分外显子上下游内含子上各设计一条gRNA,利用gRNA引导Cas9内切酶对DNA进行定点切割,从而删除52bp,使该基因下游序列发生移码,同时保留了mouse PRKDC基因的UTR区域,最终破坏PRKDC基因的表达。 该项目获得两个line,另一条line编号为T001556。这两条line均未进入表型分析。预计该品系缺失T、B细胞。

研究领域 免疫缺陷自主知识产权小鼠
应用 细胞移植反应研究 免疫缺陷病研究 炎症反应研究 移植反应研究
参考文献

Blunt T; Finnie NJ; Taccioli GE; Smith GC; Demengeot J; Gottlieb TM; Mizuta R; Varghese AJ; Alt FW; Jeggo PA; Jackson SP. 1995. Defective DNA-dependent protein kinase activity is linked to V(D)J recombination and DNA repair defects associated with the murine scid mutation. Cell 80(5):813-23. PubMed: 7889575MGI: J:30365
Blunt T; Gell D; Fox M; Taccioli GE; Lehmann AR; Jackson SP; Jeggo PA. 1996. Identification of a nonsense mutation in the carboxyl-terminal region of DNA-dependent protein kinase catalytic subunit in the scid mouse. Proc Natl Acad Sci U S A 93(19):10285-90. PubMed: 8816792MGI: J:35393
Bosma M; Schuler W; Bosma G. 1988. The scid mouse mutant. Curr Top Microbiol Immunol 137:197-202. PubMed: 3416632MGI: J:9341
Christianson SW; Shultz LD; Leiter EH. 1993. Adoptive transfer of diabetes into immunodeficient NOD-scid/scid mice. Relative contributions of CD4+ and CD8+ T-cells from diabetic versus prediabetic NOD.NON-Thy-1a donors. Diabetes 42(1):44-55. PubMed: 8093606MGI: J:34990
Hudson WA; Li Q; Le C; Kersey JH. 1998. Xenotransplantation of human lymphoid malignancies is optimized in mice with multiple immunologic defects. Leukemia 12(12):2029-33. PubMed: 9844934MGI: J:153650
Many MC; Drexhage HA; Denef JF. 1993. High frequency of thymic ectopy in thyroids from autoimmune prone nonobese diabetic female mice. Lab Invest 69(3):364-7. PubMed: 8377477MGI: J:14747
Nonoyama S; Smith FO; Bernstein ID; Ochs HD. 1993. Strain-dependent leakiness of mice with severe combined immune deficiency. J Immunol 150(9):3817-24. PubMed: 8473734MGI: J:4610
Prochazka M; Gaskins HR; Shultz LD; Leiter EH. 1992. The nonobese diabetic scid mouse: model for spontaneous thymomagenesis associated with immunodeficiency. Proc Natl Acad Sci U S A 89(8):3290-4. PubMed: 1373493MGI: J:513
Serreze DV; Leiter EH; Hanson MS; Christianson SW; Shultz LD; Hesselton RM; Greiner DL. 1995. Emv30null NOD-scid mice. An improved host for adoptive transfer of autoimmune diabetes and growth of human lymphohematopoietic cells. Diabetes 44(12):1392-8. PubMed: 7589844MGI: J:29951
Shultz LD; Schweitzer PA; Christianson SW; Gott B; Schweitzer IB; Tennent B; McKenna S; Mobraaten L; Rajan TV; Greiner DL; Leiter EH. 1995. Multiple defects in innate and adaptive immunologic function in NOD/LtSz-scid mice. J Immunol 154(1):180-91. PubMed: 7995938MGI: J:22026

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