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hCSF1 NPG 小鼠(shu)

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(cai)用转(zhuan)基因的(de)方法(fa),扩增小(xiao)鼠(shu)(shu)CSF1的(de)ATG上游1.2Kb的(de)片段(含(han)启动子(zi)),与人CSF1的(de)CDS连接,插入(ru)pCDNA3.1载体(ti)中(zhong),构建(jian)pCDNA3.1-Csf1p-hCSF1表达(da)(da)载体(ti),酶切分离表达(da)(da)载体(ti)片段,将该片段注射到NPG小(xiao)鼠(shu)(shu)的(de)原核(he)中(zhong)。在(zai)获(huo)得的(de)后代(dai)中(zhong)筛选到合(he)适表达(da)(da)量的(de)阳性小(xiao)鼠(shu)(shu)。在(zai)隔(ge)离器(qi)中(zhong),按照近交的(de)方式扩繁建(jian)立商品化的(de)hCSF1 NPG小(xiao)鼠(shu)(shu)品系(xi)。


2. 表型

在NPG小(xiao)鼠中表(biao)达(da)(da)人(ren)(ren)(ren)的(de)(de)(de)(de)(de)hCSF1细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)(bao)(bao)因子(zi)(zi)。CSF1可(ke)以(yi)促使造血(xue)干细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)(bao)(bao)调节巨噬(shi)细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)(bao)(bao)的(de)(de)(de)(de)(de)成熟、存活、粘附(fu)和(he)(he)运动(dong)。hCSF1 NPG小(xiao)鼠,表(biao)达(da)(da)合适(shi)含(han)量的(de)(de)(de)(de)(de)人(ren)(ren)(ren)CSF1蛋白,与(yu)表(biao)达(da)(da)人(ren)(ren)(ren)GM-CSF和(he)(he)IL3细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)(bao)(bao)因子(zi)(zi)的(de)(de)(de)(de)(de)NPG小(xiao)鼠一起,在移植人(ren)(ren)(ren)CD34+造血(xue)干细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)(bao)(bao)6-8周后(hou),于(yu)外(wai)周血(xue)、骨髓、胸腺和(he)(he)脾脏以(yi)及包括肺和(he)(he)肝在内的(de)(de)(de)(de)(de)非淋巴(ba)组织中,形成稳定广泛的(de)(de)(de)(de)(de)髓系(xi)和(he)(he)淋巴(ba)系(xi)细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)(bao)(bao)分化。在血(xue)液和(he)(he)组织中,可(ke)检测到粒(li)细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)(bao)(bao)分化(嗜碱性(xing)粒(li)细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)(bao)(bao)、中性(xing)粒(li)细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)(bao)(bao)和(he)(he)肥大细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)(bao)(bao)),抗原呈递细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)(bao)(bao)分化(树突状细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)(bao)(bao)和(he)(he)巨噬(shi)细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)(bao)(bao))和(he)(he)调节性(xing)T细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)(bao)(bao)群体(ti)等。表(biao)达(da)(da)人(ren)(ren)(ren)M-CSF、GM-CSF和(he)(he)人(ren)(ren)(ren)IL-3细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)(bao)(bao)因子(zi)(zi)与(yu)Hu-NPG人(ren)(ren)(ren)源化小(xiao)鼠相(xiang)比,人(ren)(ren)(ren)类造血(xue)干细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)(bao)(bao)(hsc)的(de)(de)(de)(de)(de)整体(ti)植入水平更(geng)高(gao),分化细(xi)(xi)(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)(bao)(bao)种类更(geng)多(duo)。


3. 应用领(ling)域(yu)

-人源化(hua)和癌症治疗

-人(ren)体过敏反应模型,免疫、造血(xue)移植重(zhong)建模型

-感染性疾病

-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.





hCSF1 NPG 小鼠核心技术: