Pleiotropic effects of deleterious alleles at the "motheaten" locus.
Pleiotropic effects of deleterious alleles at the "motheaten" locus.
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“受害”基因座有害等位基因的多效性。
DOI：
10.1007/978-3-642-50059-6_32
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发表时间：
1988
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
通过研究导致免疫系统发育或调节缺陷的突变，我们对基本免疫机制的理解得到了推进。我们最近回顾了30多个已知引起该系统异常的基因（Shultz和Sidman 1987）。虽然某些免疫学突变已被用作特定人类疾病的模型，但它们的主要价值是作为剖析复杂过程的工具，从而增加我们对正常和病理状态下免疫系统的理解。在这些突变中，蛾化基因座上的有害等位基因引起已知由单个基因座引起的最严重的免疫学变化。6号染色体上的隐性等位基因“蛾蚀素”（me）或“活蛾蚀素”（mev）纯合子小鼠严重免疫缺陷，并在生命早期发展为自身免疫性疾病。1965年，在杰克逊实验室的C57 BL/6 J小鼠品系中首次记录到蛾化基因座突变（绿色和Shultz 1975）。1966年，在一个携带脑积水突变的近交系中发现了一个独立的突变，命名为me 2 J。虽然突变me 2 J被用于进行连锁试验，但该原种的繁殖已停止。1980年在C57 BL/6 J株背景上发生突变。纯合子（me/me）和（mev/mev）的平均寿命分别为3周和9周（Shultz et al. 1984）。早期的实验表明有多种免疫异常。然而，这些小鼠的寿命短，很难区分免疫系统的基本缺陷和与不完全成熟和健康状况不佳相关的缺陷。
Our understanding of basic immunologic mechanisms has been advanced through the study of mutations that cause defects in the development or regulation of the immune system. We have recently reviewed more than 30 genes known to cause abnormalities in this system (Shultz and Sidman 1987). Although certain immunological mutations have served as models for specific human diseases, their chief value is as tools with which to dissect complex processes and thus increase our understanding of the immune system in normal and pathologic states. Among these mutations, deleterious alleles at the motheaten locus cause the most severe immunological changes known to be caused by a single locus. Mice homozygous for the recessive allelic genes “motheaten”(me)or “viable motheaten”(mev)on Chromosome 6 are severely immunodeficient and develop autoimmune disease early in life. The first recorded mutation at the motheaten locus occurred in 1965 in the C57BL/6J strain of mice at the Jackson Laboratory (Green and Shultz 1975). In 1966, an independent mutation namedme2J, was found in an inbred stock carrying the mutation hydrocephalus. Although the mutationme2Jwas used to carry out linkage tests, propagation of this stock has been discontinued. In 1980, themevmutation occured on the C57BL/6J strain background. Homozygotes(me/me)and(mev/mev)have a mean lifespan of 3 and 9 weeks respectively (Shultz et al. 1984). Early experimentation withme/memice indicated multiple immunologic abnormalities. However, the short lifespan of these mice made it difficult to distinguish basic defects in the immune system from those defects associated with incomplete maturation and with poor health.