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hCSF2 NPG 小(xiao)鼠

1. 基(ji)本信息(xi)

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(ji)因(yin)的(de)方法,扩增(zeng)小鼠(shu)CSF1的(de)ATG上游1.2Kb的(de)片段(含启动子),与人(ren)CSF1的(de)CDS连(lian)接,插(cha)入pCDNA3.1载体中,构(gou)建pCDNA3.1-Csf1p-hCSF1表达载体,酶切分(fen)离表达载体片段,将该片段注(zhu)射到(dao)NPG小鼠(shu)的(de)原核(he)中。在获得的(de)后代中筛选到(dao)合适表达量的(de)阳性小鼠(shu)。在隔离器中,按照近交(jiao)的(de)方式扩繁(fan)建立商品(pin)化的(de)hCSF1 NPG小鼠(shu)品(pin)系。


2. 表型

在NPG小(xiao)(xiao)鼠(shu)(shu)中(zhong)表(biao)达(da)人(ren)的hCSF1细(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)因子(zi)。CSF1可(ke)以促(cu)使造(zao)血干细(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)调节(jie)(jie)巨噬(shi)细(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)的成(cheng)熟、存活、粘附和(he)(he)运动。hCSF1 NPG小(xiao)(xiao)鼠(shu)(shu),表(biao)达(da)合适含量的人(ren)CSF1蛋白,与表(biao)达(da)人(ren)GM-CSF和(he)(he)IL3细(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)因子(zi)的NPG小(xiao)(xiao)鼠(shu)(shu)一起(qi),在移植(zhi)人(ren)CD34+造(zao)血干细(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)6-8周(zhou)(zhou)后(hou),于外周(zhou)(zhou)血、骨髓(sui)、胸腺(xian)和(he)(he)脾脏(zang)以及包括肺和(he)(he)肝在内的非淋巴组织中(zhong),形(xing)成(cheng)稳(wen)定广泛(fan)的髓(sui)系和(he)(he)淋巴系细(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)分(fen)(fen)化(hua)。在血液和(he)(he)组织中(zhong),可(ke)检(jian)测(ce)到粒细(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)分(fen)(fen)化(hua)(嗜碱性(xing)粒细(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)、中(zhong)性(xing)粒细(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)和(he)(he)肥大细(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)),抗(kang)原呈(cheng)递细(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)分(fen)(fen)化(hua)(树突(tu)状细(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)和(he)(he)巨噬(shi)细(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao))和(he)(he)调节(jie)(jie)性(xing)T细(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)群体等。表(biao)达(da)人(ren)M-CSF、GM-CSF和(he)(he)人(ren)IL-3细(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)因子(zi)与Hu-NPG人(ren)源化(hua)小(xiao)(xiao)鼠(shu)(shu)相(xiang)比,人(ren)类造(zao)血干细(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)(hsc)的整体植(zhi)入水平更(geng)高,分(fen)(fen)化(hua)细(xi)(xi)(xi)胞(bao)(bao)(bao)(bao)(bao)种类更(geng)多。


3. 应用领域

-人源(yuan)化和(he)癌症治疗(liao)

-人体过敏反(fan)应模型(xing),免疫(yi)、造血移植重建模型(xing)

-感(gan)染性疾病

-再生医学(xue)


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.