1. 基本(ben)信息
品系名称: NOD. Prkdcscid Il2rgtm1 Vst Tg(Csf1p- hCSF1) / Vst
常用名: hCSF1-NPG; hCSF1 NPG
背景: NOD-scid/NcrCrl
毛色: 白色
品系建立:
采用转(zhuan)基因的(de)(de)(de)方法,扩增(zeng)小鼠CSF1的(de)(de)(de)ATG上游1.2Kb的(de)(de)(de)片段(含(han)启动子),与人CSF1的(de)(de)(de)CDS连接,插入pCDNA3.1载(zai)体(ti)中(zhong),构建(jian)(jian)pCDNA3.1-Csf1p-hCSF1表(biao)(biao)达(da)载(zai)体(ti),酶(mei)切分离表(biao)(biao)达(da)载(zai)体(ti)片段,将该(gai)片段注(zhu)射到NPG小鼠的(de)(de)(de)原(yuan)核中(zhong)。在获得的(de)(de)(de)后代中(zhong)筛选(xuan)到合适表(biao)(biao)达(da)量的(de)(de)(de)阳性(xing)小鼠。在隔离器(qi)中(zhong),按照近交的(de)(de)(de)方式(shi)扩繁建(jian)(jian)立商品(pin)化(hua)的(de)(de)(de)hCSF1 NPG小鼠品(pin)系。
2. 表型(xing)
在(zai)NPG小鼠(shu)中(zhong)表(biao)达(da)人(ren)的hCSF1细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)因(yin)子。CSF1可以(yi)促使(shi)造血干(gan)细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)调节巨噬(shi)细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)的成(cheng)熟、存活(huo)、粘附和(he)(he)运动。hCSF1 NPG小鼠(shu),表(biao)达(da)合适含量的人(ren)CSF1蛋白,与(yu)表(biao)达(da)人(ren)GM-CSF和(he)(he)IL3细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)因(yin)子的NPG小鼠(shu)一起,在(zai)移植(zhi)人(ren)CD34+造血干(gan)细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)6-8周(zhou)(zhou)后(hou),于外周(zhou)(zhou)血、骨髓、胸腺和(he)(he)脾脏以(yi)及包括(kuo)肺和(he)(he)肝在(zai)内(nei)的非淋(lin)(lin)巴(ba)组(zu)织中(zhong),形成(cheng)稳定广泛的髓系和(he)(he)淋(lin)(lin)巴(ba)系细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)分(fen)(fen)化。在(zai)血液和(he)(he)组(zu)织中(zhong),可检测到粒细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)分(fen)(fen)化(嗜(shi)碱(jian)性(xing)粒细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)、中(zhong)性(xing)粒细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)和(he)(he)肥大细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)),抗原呈递细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)分(fen)(fen)化(树突状(zhuang)细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)和(he)(he)巨噬(shi)细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao))和(he)(he)调节性(xing)T细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)群体(ti)等。表(biao)达(da)人(ren)M-CSF、GM-CSF和(he)(he)人(ren)IL-3细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)因(yin)子与(yu)Hu-NPG人(ren)源化小鼠(shu)相比,人(ren)类造血干(gan)细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(hsc)的整(zheng)体(ti)植(zhi)入水平更(geng)高(gao),分(fen)(fen)化细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)种类更(geng)多(duo)。
3. 应用领域
-人源化和(he)癌症治疗
-人体(ti)过(guo)敏(min)反应模型,免疫、造血(xue)移植重建模型
-感染(ran)性疾病
-再生医(yi)学
4. 参考文(wen)献
(1)Rathinam C; Poueymirou WT; Rojas J; Murphy AJ; Valenzuela DM; Yancopoulos GD; Rongvaux A; Eynon EE; Manz MG; Flavell RA. 2011. Efficient differentiation and function of human macrophages in humanized CSF-1 mice. Blood 118(11):3119-28.
(2)Wunderlich M; Chou FS; Link KA; Mizukawa B; Perry RL; Carroll M; Mulloy JC. 2010. AML xenograft efficiency is significantly improved in NOD/SCID-IL2RG mice constitutively expressing human SCF, GM-CSF and IL-3. Leukemia 24(10):1785-8.
(3)Ito R, Takahashi T, Katano I, Kawai K, Kamisako T, Ogura T, Ida-Tanaka M, Suemizu H, Nunomura S, Ra C, Mori A, Aiso S, Ito M. (2013) Establishment of a human allergy model using human IL-3/GM-CSF-transgenic NOG mice. J Immunol.191(6):2890-9.