Atm-deficient mice: A paradigm of ataxia telangiectasia
Atm-deficient mice: A paradigm of ataxia telangiectasia
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DOI：
10.1016/s0092-8674(00)80086-0
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发表时间：
1996-07-12
期刊：
影响因子：
64.5
通讯作者：
WynshawBoris, A
中科院分区：
文献类型：
--
作者：
Barlow, C;Hirotsune, S;WynshawBoris, A
通过基因靶向破坏Atm基因座来创建共济失调毛细血管扩张症的鼠模型。Atm等位基因纯合子小鼠表现出生长迟缓、神经功能障碍、继发于缺乏成熟配子的雄性和雌性不育、T淋巴细胞成熟缺陷以及对γ射线的极端敏感性。大多数动物在2至4月龄之间发生恶性胸腺淋巴瘤。在其中一个肿瘤中检测到几种染色体异常。这些小鼠的成纤维细胞生长缓慢，并表现出异常的辐射诱导的G1检查点功能。ATM破坏小鼠重演共济失调毛细血管扩张症在人类的表型，提供了一个哺乳动物模型，在其中研究这种多效性疾病的病理生理学。
A murine model of ataxia telangiectasia was created by disrupting the Atm locus via gene targeting. Mice homozygous for the disrupted Atm allele displayed growth retardation, neurologic dysfunction, male and female infertility secondary to the absence of mature gametes, defects in T lymphocyte maturation, and extreme sensitivity to gamma-irradiation. The majority of animals developed malignant thymic lymphomas between 2 and 4 months of age. Several chromosomal anomalies were detected in one of these tumors. Fibroblasts from these mice grew slowly and exhibited abnormal radiation-induced G1 checkpoint function. Atm-disrupted mice recapitulate the ataxia telangiectasia phenotype in humans, providing a mammalian model in which to study the pathophysiology of this pleiotropic disorder.