Molecular pathology of severe combined immunodeficiency in mice, horses, and dogs
Molecular pathology of severe combined immunodeficiency in mice, horses, and dogs
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DOI：
10.1354/vp.41-2-95
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发表时间：
2004-03-01
影响因子：
2.4
通讯作者：
Perryman, LE
中科院分区：
文献类型：
--
作者：
Perryman, LE
严重联合免疫缺陷（SCID）是人类、小鼠、马和狗的一种遗传性疾病，其中受影响的个体不能产生抗原特异性免疫应答。当淋巴细胞前体细胞由于重组酶激活基因1和2或编码脱氧核糖核酸（DNA）依赖性蛋白激酶（DNA-PK）的基因内的突变而不能分化为成熟淋巴细胞时，就会发生这种情况。当分化的淋巴细胞由于白细胞介素（IL）的细胞表面受体缺陷而不能完成信号转导途径时也会发生。BALB/c小鼠DNA-PKcs的自发突变导致SCID，RAG 1和RAG 2的实验诱导突变也是如此。马的SCID是由DNA-PKcs的自发突变引起的。两种分子机制解释了行动者的SCID。杰克罗素梗在DNA-PKcs基因中有一个突变，而开衫威尔士柯基犬和巴吉度猎犬在编码γ链的基因中有不同的缺陷，这是IL-2受体所共有的。-4. -7-9 -15和-21靶基因内突变的位置影响在受影响动物中观察到的疾病谱。
Severe combined immunodeficiency (SCID) is an inherited disorder of humans, mice, horses, and dogs, in which affected individuals are incapable of generating antigen-specific immune responses. It occurs when lymphocyte precursors fail to differentiate into mature lymphocytes because of mutations within recombinase-activating genes 1 and 2 or within the genes encoding deoxyribonucleic acid (DNA)-dependent protein kinase (DNA-PK). It also occurs when differentiated lymphocytes are incapable of completing signal transduction pathways because of defects in cell surface receptors for interleukins (IL). A spontaneous mutation in DNA-PKcs of BALB/c mice results in SCID, as do experimentally induced mutations in RAG1 and RAG2. SCID in horses results from a spontaneous mutation in DNA-PKcs. Two molecular mechanisms account for SCID in doers. Jack Russell Terriers have a mutation within the DNA-PKcs gene, whereas Cardigan Welsh Corgi and Basset Hound have different defects in the gene encoding the gamma chain that is common to the receptors for IL-2. -4. -7, -9. -15, and -21. The location of the mutation within target genes influences the spectrum of diseases observed in affected animals.