1. 基(ji)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)方法(fa),扩增小(xiao)鼠CSF1的(de)ATG上游1.2Kb的(de)片段(含(han)启动子),与人CSF1的(de)CDS连接,插入(ru)pCDNA3.1载体(ti)中(zhong),构建pCDNA3.1-Csf1p-hCSF1表达(da)载体(ti),酶切分离(li)表达(da)载体(ti)片段,将(jiang)该片段注射到NPG小(xiao)鼠的(de)原核中(zhong)。在获得(de)的(de)后代(dai)中(zhong)筛选到合(he)适(shi)表达(da)量的(de)阳性小(xiao)鼠。在隔离(li)器(qi)中(zhong),按照近交的(de)方式扩繁建立商品化的(de)hCSF1 NPG小(xiao)鼠品系(xi)。
2. 表(biao)型
在(zai)NPG小(xiao)鼠中(zhong)表(biao)(biao)达(da)(da)人(ren)(ren)的(de)(de)hCSF1细(xi)(xi)(xi)(xi)胞(bao)(bao)因(yin)子(zi)(zi)。CSF1可以促(cu)使(shi)造(zao)血(xue)干细(xi)(xi)(xi)(xi)胞(bao)(bao)调节巨噬细(xi)(xi)(xi)(xi)胞(bao)(bao)的(de)(de)成熟、存活、粘(zhan)附和(he)(he)运动。hCSF1 NPG小(xiao)鼠,表(biao)(biao)达(da)(da)合适含量(liang)的(de)(de)人(ren)(ren)CSF1蛋白,与表(biao)(biao)达(da)(da)人(ren)(ren)GM-CSF和(he)(he)IL3细(xi)(xi)(xi)(xi)胞(bao)(bao)因(yin)子(zi)(zi)的(de)(de)NPG小(xiao)鼠一(yi)起,在(zai)移植人(ren)(ren)CD34+造(zao)血(xue)干细(xi)(xi)(xi)(xi)胞(bao)(bao)6-8周后,于外周血(xue)、骨髓、胸(xiong)腺(xian)和(he)(he)脾脏以及包括肺和(he)(he)肝在(zai)内的(de)(de)非淋(lin)巴组织(zhi)中(zhong),形成稳(wen)定(ding)广(guang)泛的(de)(de)髓系和(he)(he)淋(lin)巴系细(xi)(xi)(xi)(xi)胞(bao)(bao)分(fen)化(hua)。在(zai)血(xue)液和(he)(he)组织(zhi)中(zhong),可检(jian)测到粒(li)细(xi)(xi)(xi)(xi)胞(bao)(bao)分(fen)化(hua)(嗜碱性粒(li)细(xi)(xi)(xi)(xi)胞(bao)(bao)、中(zhong)性粒(li)细(xi)(xi)(xi)(xi)胞(bao)(bao)和(he)(he)肥(fei)大细(xi)(xi)(xi)(xi)胞(bao)(bao)),抗原呈(cheng)递细(xi)(xi)(xi)(xi)胞(bao)(bao)分(fen)化(hua)(树突状细(xi)(xi)(xi)(xi)胞(bao)(bao)和(he)(he)巨噬细(xi)(xi)(xi)(xi)胞(bao)(bao))和(he)(he)调节性T细(xi)(xi)(xi)(xi)胞(bao)(bao)群体等。表(biao)(biao)达(da)(da)人(ren)(ren)M-CSF、GM-CSF和(he)(he)人(ren)(ren)IL-3细(xi)(xi)(xi)(xi)胞(bao)(bao)因(yin)子(zi)(zi)与Hu-NPG人(ren)(ren)源(yuan)化(hua)小(xiao)鼠相比,人(ren)(ren)类(lei)造(zao)血(xue)干细(xi)(xi)(xi)(xi)胞(bao)(bao)(hsc)的(de)(de)整体植入水平更高,分(fen)化(hua)细(xi)(xi)(xi)(xi)胞(bao)(bao)种类(lei)更多。
3. 应用领(ling)域
-人源化(hua)和癌(ai)症治(zhi)疗(liao)
-人体过(guo)敏(min)反应(ying)模型,免疫、造血移植重建(jian)模型
-感染性疾病
-再(zai)生医学
4. 参(can)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.