Mice lacking all conventional MHC class II genes
Mice lacking all conventional MHC class II genes
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DOI：
10.1073/pnas.96.18.10338
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发表时间：
1999-08-31
影响因子：
11.1
通讯作者：
Fugger, L
中科院分区：
文献类型：
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作者：
Madsen, L;Labrecque, N;Fugger, L
主要组织相容性复合体II类（MHC - II）分子在T细胞库的选择、适应性免疫应答的建立和调节以及自身免疫偏离中起着核心作用。我们通过同源重组和Cre重组酶介导的切除技术，对整个II类区域进行了大片段（80千碱基）缺失操作，从而培育出了缺失所有四种经典鼠类MHC - II基因的基因敲除小鼠（MHCIIΔ/Δ小鼠）。这些小鼠的免疫系统紊乱情况与Aar和AP基因敲除动物相似，特别是在胸腺和脾脏中缺乏CD4⁺淋巴细胞。在MHCIIΔ/Δ小鼠中未观察到新的解剖学或生理学异常。由于这些动物缺乏所有经典的MHC - II链，甚至是未配对的链，它们是来自其他物种的MHC - II转基因的良好受体，避免了MHC - II链的种间交叉配对问题。因此，它们对于构建人类MHC - II相关自身免疫疾病的“人源化”小鼠模型应该具有极高的价值。
MHC class II (MHC-II) molecules play a central role in the selection of the T cell repertoire, in the establishment and regulation of the adaptive immune response, and in autoimmune deviation. We have generated knockout mice lacking all four of the classical murine MHC-II. genes (MHCIIDelta/Delta mice), via a large (80-kilobase) deletion of the entire class II region that was engineered by homologous recombination and Cre recombinase-mediated excision, These mice feature immune system perturbations like those of Aar and AP knockout animals, notably a dearth of CD4(+) lymphocytes in the thymus and spleen. No new anatomical or physiological abnormalities were observed in MHCIIDelta/Delta mice. Because these animals are devoid of all classical MNC-II chains, even unpaired chains, they make excellent recipients for MHC-II transgenes from other species, avoiding the problem of interspecies cross-pairing of MHC-II chains. Therefore, they should be invaluable for engineering "humanized" mouse models of human MHC-LI-associated autoimmune disorders.