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: NOD-scid/NcrCrl
毛色: 白色
品系建立:
采用转基因的(de)方(fang)法,扩增(zeng)小鼠(shu)CSF1的(de)ATG上游1.2Kb的(de)片段(duan)(含(han)启动子),与人CSF1的(de)CDS连接(jie),插入(ru)pCDNA3.1载(zai)体(ti)中(zhong),构建pCDNA3.1-Csf1p-hCSF1表(biao)(biao)达(da)载(zai)体(ti),酶切分离(li)表(biao)(biao)达(da)载(zai)体(ti)片段(duan),将该片段(duan)注射到(dao)NPG小鼠(shu)的(de)原核中(zhong)。在获(huo)得的(de)后(hou)代中(zhong)筛(shai)选(xuan)到(dao)合适表(biao)(biao)达(da)量的(de)阳性小鼠(shu)。在隔离(li)器中(zhong),按照(zhao)近交(jiao)的(de)方(fang)式扩繁(fan)建立商品化的(de)hCSF1 NPG小鼠(shu)品系。
2. 表型
在(zai)(zai)NPG小鼠中表达人(ren)的(de)(de)hCSF1细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)因子(zi)。CSF1可(ke)以(yi)促使造血干细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)调节巨噬细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)的(de)(de)成熟、存活(huo)、粘附和(he)(he)运(yun)动(dong)。hCSF1 NPG小鼠,表达合适含(han)量的(de)(de)人(ren)CSF1蛋白(bai),与表达人(ren)GM-CSF和(he)(he)IL3细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)因子(zi)的(de)(de)NPG小鼠一起(qi),在(zai)(zai)移(yi)植人(ren)CD34+造血干细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)6-8周后(hou),于外周血、骨髓、胸腺和(he)(he)脾脏以(yi)及包括肺和(he)(he)肝在(zai)(zai)内的(de)(de)非淋(lin)巴(ba)组(zu)织(zhi)(zhi)中,形(xing)成稳定(ding)广泛的(de)(de)髓系和(he)(he)淋(lin)巴(ba)系细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)分(fen)化(hua)。在(zai)(zai)血液和(he)(he)组(zu)织(zhi)(zhi)中,可(ke)检测到(dao)粒(li)细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)分(fen)化(hua)(嗜碱性(xing)粒(li)细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)、中性(xing)粒(li)细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)和(he)(he)肥大细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)),抗原呈递(di)细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)分(fen)化(hua)(树突状细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)和(he)(he)巨噬细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao))和(he)(he)调节性(xing)T细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)群(qun)体(ti)等(deng)。表达人(ren)M-CSF、GM-CSF和(he)(he)人(ren)IL-3细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)因子(zi)与Hu-NPG人(ren)源化(hua)小鼠相(xiang)比,人(ren)类造血干细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(hsc)的(de)(de)整体(ti)植入水平更高,分(fen)化(hua)细(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)种类更多。
3. 应用(yong)领域(yu)
-人源(yuan)化和癌症治疗
-人(ren)体过敏(min)反应模型,免疫(yi)、造血(xue)移植重建模型
-感染性疾病
-再生(sheng)医学
4. 参考文献
(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.