1. 基本信息
品系名称(cheng):NOD-Rag2tm1 Il2rgtm1 /Vst
常用(yong)名:NRG /Vst; NOD rag2 gamma c
背景:NOD
毛色:白色
品(pin)系(xi)建立:
采(cai)用基(ji)因编辑(ji)技术获(huo)得(de)Rag2 (recombination activating gene 2)基(ji)因敲(qiao)(qiao)(qiao)除的C57BL/6小鼠(shu)(shu),然(ran)后(hou)与NPG/Vst小鼠(shu)(shu)杂交。在(zai)后(hou)代(dai)中筛选Rag2敲(qiao)(qiao)(qiao)除、Il2rg敲(qiao)(qiao)(qiao)除、NOD型(xing)Sirpa以及scid基(ji)因非纯合(he)的个体,再通过杂合(he)互(hu)配的方式获(huo)得(de)纯合(he)NOD rag2 gamma(NRG)小鼠(shu)(shu)(JAX的NRG小鼠(shu)(shu)是rag1基(ji)因敲(qiao)(qiao)(qiao)除,二(er)者表(biao)型(xing)类型(xing))。Rag2突变使(shi)小鼠(shu)(shu)T和B细(xi)胞缺失;Il2rg敲(qiao)(qiao)(qiao)除小鼠(shu)(shu)引起(qi)NK细(xi)胞数(shu)量(liang)减(jian)少,活性丧失。在(zai)隔离(li)器中,按照近交的方式扩繁(fan)建立商品化的NRG/Vst小鼠(shu)(shu)品系。
2 .表型(xing)分析
与NPG(NOD-scid gamma)小(xiao)鼠相比, NRG小(xiao)鼠同样(yang)具(ju)有T细胞(bao)、B细胞(bao)、NK细胞(bao)、巨噬(shi)细胞(bao)的缺陷,因而可以作为(wei)高度(du)免疫缺陷小(xiao)鼠用于建(jian)立异种组织和(he)肿瘤移植(zhi)(zhi)模(mo)型。但因为(wei)NRG小(xiao)鼠无scid基因突变,更(geng)(geng)耐辐照和(he)更(geng)(geng)能耐受放疗药物组合(he)的药效(xiao)(xiao)试验(yan)。NRG /Vst小(xiao)鼠可以高效(xiao)(xiao)定植(zhi)(zhi)人CD34+ 造(zao)血干(gan)细胞(bao)(HSC)和(he)病(bing)人来(lai)源(yuan)(yuan)的肿瘤移植(zhi)(zhi)物(PDX),是一种理想(xiang)的人源(yuan)(yuan)化基础模(mo)型小(xiao)鼠
(1)NRG /Vst与NPG小鼠相比(bi),更(geng)耐辐(fu)照。
图1 不同剂量辐(fu)照(zhao)后,NRG小鼠存活曲(qu)线,可见NRG /Vst小鼠可以耐受(shou)3~4 Gy的(de)剂量。
3. 应用领域(yu)
-异种(zhong)肿(zhong)瘤移植模型GvHD体内机理研(yan)究(jiu)
-GvHD模型
-肿瘤放疗实验研究
-新的人源化动(dong)物模型研发
4. 参(can)考文献(xian)
(1)Pearson T, Shultz LD, Miller D, etal. Non-obese diabetic-recombination activating gene-1 (NOD-Rag1 null) interleukin (IL)-2 receptor common gamma chain (IL2r gamma null) null mice: a radioresistant model for human lymphohaematopoietic engraftment. Clin Exp Immunol. 2008 Nov;154(2):270-84.
(2), , , et al. Parameters for establishing humanized mouse models to study human immunity: analysis of human hematopoietic stem cell engraftment in three immunodeficient strains of mice bearing the IL2rgamma(null) mutation. 2010 Apr;135(1):84-98.
(3)Maykel J, Liu JH, Li H, Shultz LD, et al. NOD-scidIl2rg (tm1Wjl) and NOD-Rag1 (null) Il2rg (tm1Wjl) : a model for stromal cell-tumor cell interaction for human colon cancer. Dig Dis Sci. 2014 Jun;59(6):1169-79. doi: 10.1007/s10620-014-3168-5. Epub 2014 May 6.