Pleiotropic mutations causing abnormalities in the murine immune system and the skin.
Pleiotropic mutations causing abnormalities in the murine immune system and the skin.
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多效性突变导致小鼠免疫系统和皮肤异常。
DOI：
10.1159/000413486
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
Shultz,LD
中科院分区：
文献类型：
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作者：
Shultz,LD
通过对实验动物遗传决定的免疫功能障碍的研究，促进了对人类免疫缺陷和自身免疫的基本机制的研究。我们目前对这种功能障碍的细胞基础的理解，特别是与自身免疫性疾病的关系，在很大程度上来自于使用NZB小鼠品系和（NZB× NZW）F * 杂交小鼠的实验。这些小鼠具有涉及T细胞、B细胞和巨噬细胞的功能缺陷，导致广泛的免疫学异常，包括多克隆IG产生、自身抗体和循环以及组织沉积的免疫复合物[1]。不幸的是，NZB小鼠自身免疫性疾病的遗传机制非常复杂，依赖于多个遗传位点[2]。通过检测这些小鼠与“非自身免疫性”品系小鼠（如C57 BL/6 J）之间的等位基因差异，可以设想确定NZB小鼠免疫性疾病遗传基础的困难。这两个菌株已分型为128个多态性位点。这种分型揭示了NZB和C57 BL/6 J小鼠之间的43个等位基因差异[Roderick，个人交流]。因此，这两种完全不同的菌株的基因组的约34%在分型位点上不同，并且估计表明存在约100，000个基因。这些计算表明，NZB和C57 BL/6小鼠可能在34，000个基因座上存在差异。因为只有30%的老鼠
Research into the basic mechanisms underlying immunodeficiency and autoimmunity in man has been facilitated by the study of genetically determined immunologic dysfunction in experimental animals. Our current understanding of the cellular basis of such dysfunction, particularly in relationship to autoimmune disease, has come in large part from experiments using strain NZB mice and the (NZB× NZW) F₁ hybrid. These mice have functional defects involving T cells, B cells, and macrophages resulting in a wide spectrum of immunologic abnormalities including polyclonal Ig production, autoantibodies, and circulating as well as tissue-deposited immune complexes [1]. Unfortunately, the genetic mechanisms of autoim-mune disease in NZB mice are extremely complex and depend on multiple genetic loci [2].The difficulty in determining the genetic bases for immunologic disease in NZB mice can be envisaged by examining allelic differences between these mice and mice of a'nonautoimmune'strain, such as C57BL/6J. Both of these strains have been typed for 128 polymorphic loci. Such typing has revealed 43 allelic differences between NZB and C57BL/6J mice [Roderick, personal communication]. Thus, approximately 34% of the genome of these two disparate strains differ at typed loci, and estimates indicate the presence of approximately 100,000 genes. These calculations suggest that NZB and C57BL/6 mice could differ at 34,000 loci. Since only 30% of the mouse