1. 基本信息
品(pin)系名称:NOD. Prkdcscid Il2rgtm1 Vst Tg(Csf1p- hCSF1) / Vst
常用(yong)名:hCSF1-NPG; hCSF1 NPG
背(bei)景:NOD-scid/NcrCrl
毛色:白色
品系建(jian)立(li):
采用转(zhuan)基因的(de)(de)(de)(de)方法,扩增小(xiao)(xiao)鼠CSF1的(de)(de)(de)(de)ATG上游(you)1.2Kb的(de)(de)(de)(de)片段(duan)(含(han)启动(dong)子),与人CSF1的(de)(de)(de)(de)CDS连接,插入pCDNA3.1载(zai)体(ti)中(zhong)(zhong),构建(jian)(jian)pCDNA3.1-Csf1p-hCSF1表达(da)载(zai)体(ti),酶切分离表达(da)载(zai)体(ti)片段(duan),将该片段(duan)注(zhu)射到NPG小(xiao)(xiao)鼠的(de)(de)(de)(de)原核中(zhong)(zhong)。在获得的(de)(de)(de)(de)后代(dai)中(zhong)(zhong)筛选到合适(shi)表达(da)量(liang)的(de)(de)(de)(de)阳性小(xiao)(xiao)鼠。在隔离器中(zhong)(zhong),按照(zhao)近交的(de)(de)(de)(de)方式扩繁建(jian)(jian)立(li)商(shang)品化的(de)(de)(de)(de)hCSF1 NPG小(xiao)(xiao)鼠品系(xi)。
2. 表型(xing)
在(zai)NPG小鼠(shu)中(zhong)(zhong)(zhong)表达(da)(da)人(ren)(ren)的(de)hCSF1细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)因(yin)子(zi)(zi)。CSF1可以促使造(zao)血干细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)调(diao)节(jie)巨(ju)(ju)噬(shi)细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)的(de)成(cheng)熟、存活、粘(zhan)附和(he)(he)运动(dong)。hCSF1 NPG小鼠(shu),表达(da)(da)合适含量(liang)的(de)人(ren)(ren)CSF1蛋(dan)白(bai),与表达(da)(da)人(ren)(ren)GM-CSF和(he)(he)IL3细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)因(yin)子(zi)(zi)的(de)NPG小鼠(shu)一起,在(zai)移植人(ren)(ren)CD34+造(zao)血干细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)6-8周后,于外(wai)周血、骨髓、胸腺(xian)和(he)(he)脾脏以及包括肺和(he)(he)肝在(zai)内的(de)非淋巴组(zu)织中(zhong)(zhong)(zhong),形成(cheng)稳定广泛的(de)髓系和(he)(he)淋巴系细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)分化(hua)。在(zai)血液和(he)(he)组(zu)织中(zhong)(zhong)(zhong),可检测(ce)到粒细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)分化(hua)(嗜碱性(xing)粒细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)、中(zhong)(zhong)(zhong)性(xing)粒细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)和(he)(he)肥大细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)),抗原呈(cheng)递细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)分化(hua)(树突状细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)和(he)(he)巨(ju)(ju)噬(shi)细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao))和(he)(he)调(diao)节(jie)性(xing)T细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)群体等。表达(da)(da)人(ren)(ren)M-CSF、GM-CSF和(he)(he)人(ren)(ren)IL-3细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)因(yin)子(zi)(zi)与Hu-NPG人(ren)(ren)源化(hua)小鼠(shu)相(xiang)比,人(ren)(ren)类造(zao)血干细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(hsc)的(de)整体植入水平更高,分化(hua)细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)种类更多。
3. 应用领(ling)域
-人源化和癌(ai)症治疗
-人体过敏(min)反应模(mo)型,免疫、造血(xue)移植重(zhong)建模(mo)型
-感染性(xing)疾病(bing)
-再生医学
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.