Pleiotropic defects in ataxia-telangiectasia protein-deficient mice
Pleiotropic defects in ataxia-telangiectasia protein-deficient mice
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DOI：
10.1073/pnas.93.23.13084
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发表时间：
1996-11-12
影响因子：
11.1
通讯作者：
Leder, P
中科院分区：
文献类型：
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作者：
Elson, A;Wang, YQ;Leder, P
我们通过使用基因靶向产生不表达Atm蛋白的小鼠，建立了共济失调血管扩张症的小鼠模型。Atm缺陷小鼠生长迟缓，不产生成熟精子，并在T细胞成熟方面表现出严重缺陷，同时继续发展胸腺瘤。Atm缺陷的成纤维细胞在培养中生长不良，并显示出高水平的双链染色体断裂，Atm缺陷的胸腺细胞在体外发生自发凋亡显著多于对照组。缺乏atm的小鼠表现出许多与共济失调血管扩张症患者和他们的细胞相同的症状。此外，我们证明了Atm蛋白作为两个离散的分子物种存在，并且这些分子中的一个或多个的丢失可能导致疾病的发展。
We have generated a mouse model for ataxiatelangiectasia by using gene targeting to generate mice that do not express the Atm protein. Atm-deficient mice are retarded in growth, do not produce mature sperm, and exhibit severe defects in T cell maturation while going on to develop thymomas. Atm-deficient fibroblasts grow poorly in culture and display a high level of double-stranded chromosome breaks, Atm-deficient thymocytes undergo spontaneous apoptosis in vitro significantly more than controls. Atm-deficient mice then exhibit many of the same symptoms found in ataxiatelangiectasia patients and in cells derived from them. Furthermore, we demonstrate that the Atm protein exists as two discrete molecular species, and that loss of one or of bath of these can lead to the development of the disease.