‘Wasted’, a new mutant of the mouse with abnormalities characteristic of ataxia telangiectasia

Abstract

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 neoplasms^1–3. 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 and γ ray-induced chromosomal damage.