1. 基本信息
品系名称:NOD. Prkdcscid Il2rgtm1 Vst Tg(Csf1p- hCSF1) / Vst
常用名:hCSF1-NPG; hCSF1 NPG
背景(jing):NOD-scid/NcrCrl
毛色:白(bai)色
品(pin)系建立:
采用转基因(yin)的(de)方法(fa),扩增小(xiao)鼠(shu)CSF1的(de)ATG上游1.2Kb的(de)片段(duan)(含启(qi)动(dong)子),与(yu)人(ren)CSF1的(de)CDS连接,插入pCDNA3.1载体(ti)(ti)中(zhong)(zhong),构建pCDNA3.1-Csf1p-hCSF1表(biao)达载体(ti)(ti),酶切分离表(biao)达载体(ti)(ti)片段(duan),将(jiang)该片段(duan)注射到NPG小(xiao)鼠(shu)的(de)原核中(zhong)(zhong)。在获得的(de)后代中(zhong)(zhong)筛选到合适表(biao)达量的(de)阳性(xing)小(xiao)鼠(shu)。在隔(ge)离器中(zhong)(zhong),按照近(jin)交的(de)方式(shi)扩繁建立商品化的(de)hCSF1 NPG小(xiao)鼠(shu)品系。
2. 表型(xing)
在NPG小鼠(shu)中(zhong)(zhong)(zhong)表(biao)(biao)达人(ren)的(de)hCSF1细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)因(yin)子(zi)。CSF1可以促(cu)使造血(xue)(xue)(xue)干(gan)细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)调节巨(ju)噬细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)的(de)成(cheng)熟、存活、粘附和运动。hCSF1 NPG小鼠(shu),表(biao)(biao)达合(he)适含量的(de)人(ren)CSF1蛋白,与(yu)表(biao)(biao)达人(ren)GM-CSF和IL3细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)因(yin)子(zi)的(de)NPG小鼠(shu)一起,在移植人(ren)CD34+造血(xue)(xue)(xue)干(gan)细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)6-8周后(hou),于外周血(xue)(xue)(xue)、骨髓(sui)、胸腺和脾脏(zang)以及包括肺和肝(gan)在内的(de)非淋(lin)(lin)巴组织(zhi)中(zhong)(zhong)(zhong),形成(cheng)稳(wen)定广泛的(de)髓(sui)系(xi)和淋(lin)(lin)巴系(xi)细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)分(fen)(fen)化(hua)。在血(xue)(xue)(xue)液和组织(zhi)中(zhong)(zhong)(zhong),可检测到粒细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)分(fen)(fen)化(hua)(嗜碱性粒细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)、中(zhong)(zhong)(zhong)性粒细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)和肥大(da)细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)),抗原呈递细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)分(fen)(fen)化(hua)(树突状(zhuang)细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)和巨(ju)噬细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao))和调节性T细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)群(qun)体等。表(biao)(biao)达人(ren)M-CSF、GM-CSF和人(ren)IL-3细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)因(yin)子(zi)与(yu)Hu-NPG人(ren)源(yuan)化(hua)小鼠(shu)相比,人(ren)类(lei)造血(xue)(xue)(xue)干(gan)细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(hsc)的(de)整(zheng)体植入水平更(geng)高(gao),分(fen)(fen)化(hua)细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)种类(lei)更(geng)多。
3. 应(ying)用(yong)领(ling)域(yu)
-人(ren)源(yuan)化(hua)和癌(ai)症治疗
-人体(ti)过敏反应(ying)模(mo)型,免疫(yi)、造血移植重建(jian)模(mo)型
-感染(ran)性疾病
-再生医学(xue)
4. 参(can)考文献
(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.