WASTED, A NEW MUTANT OF THE MOUSE WITH ABNORMALITIES CHARACTERISTIC OF ATAXIA TELANGIECTASIA
WASTED, A NEW MUTANT OF THE MOUSE WITH ABNORMALITIES CHARACTERISTIC OF ATAXIA TELANGIECTASIA
复制标题
DOI：
10.1038/297402a0
复制
发表时间：
1982-01-01
期刊：
影响因子：
64.8
通讯作者：
COMAN, DR
中科院分区：
文献类型：
--
作者：
SHULTZ, LD;SWEET, HO;COMAN, DR
对实验动物单基因突变的研究促进了对复杂多系统疾病发展的基本机制的研究。共济失调毛细血管扩张症是一种多方面的遗传决定性疾病，目前尚无动物模型描述。它发生在儿童中，其特征在于不同程度的免疫缺陷、小脑共济失调、眼皮肤毛细血管扩张、慢性鼻窦炎、内分泌异常、染色体畸变和肿瘤的高发病率1 -3。虽然临床表现已被很好地记录，但疾病的原因尚不清楚。共济失调毛细血管扩张症基因的多效性是非常复杂的。这种疾病的许多方面，包括胚胎发育中的组织分化障碍，不适合直接研究，因此共济失调毛细血管扩张症的动物模型将是有价值的，在阐明潜在的机制，并在开发有效的预防或治疗措施。我们最近发现了一种自发突变的小鼠，称为“wasted”（wst），表现出类似于共济失调毛细血管扩张症的病理变化。这种突变可以在3周龄时通过神经系统异常识别。我们在这里报告，受影响的动物表现出中枢神经和淋巴系统的病理变化，并表现出高度的自发性和γ射线诱导的染色体损伤。
Research into the basic mechanisms underlying the development of complex multi-system diseases has been facilitated by the study of single gene mutations in experimental animals. Ataxia telangiectasia is such a multifaceted genetically determined disease for which no animal model has been described. It occurs in children and is characterized by varying degrees of immunodeficiency, cerebellar ataxia, oculocutaneous telangiectasia, chronic sinopulmonary disease, endocrine abnormalities, chromosomal aberrations, and a high incidence of neoplasms1–3. Although the clinical manifestations have been well documented, the cause of the disease is unknown. The pleiotropic nature of the ataxia telangiectasia gene is very complex. Many aspects of this disease, including impairment of tissue differentiation in embryological development are not amenable to direct study, thus an animal model for ataxia telangiectasia would be valuable in elucidating the underlying mechanisms, and in developing effective preventive or therapeutic measures. We have recently found a spontaneous mutation of the mouse called‘wasted’(wst) that shows pathological changes similar to those of ataxia telangiectasia. This mutation can be recognized at 3 weeks of age by neurological abnormalities. We report here that affected animals show pathological changes in the central nervous and lymphoid systems and exhibit a high degree of spontaneous andγray-induced chromosomal damage.