The wasted mutant mouse. II. Immunological abnormalities in a mouse described as a model of ataxia-telangiectasia.

摘要

Ataxia-telangiectasia (AT) is a complex multiparametric disease associating oculocutaneous telangiectasias, cerebellar ataxia, elevated chromosomal aberration frequency and varied degrees of immunodeficiency. Recently a wasted mutant mouse (wst) has been described as an animal model of AT. We have looked in the wasted mutants for the presence of immune and endocrine abnormalities characteristic of AT. In contrast to the T cell immunodeficiency in AT, wasted mutants had a marked hypoplasia of all lymphoid organs, which affected both T and B lymphocyte subsets. The marked thymic atrophy appearing at the final stage of their disease did not modify the endocrine function of the thymic epithelium which produced normal levels of the thymic hormone thymulin. Although in vitro interleukin 2 (IL-2) production by splenic T cells in response to Con A was markedly diminished, these mice presented normal T and B cell proliferative responses to mitogens. Finally, no significant increase in serum alpha-fetoprotein level (a typical marker of AT) was found throughout the course of the disease. Although by many aspects, i.e. neurological disorder, chromosomal aberrations and early death, wasted mice presented similarities with human AT, major discrepancies in the typical features of immune abnormalities were found between the mouse model and the human disease.