Pleiotropic defects in ataxia-telangiectasia protein-deficient mice.

Authors: Elson A; Wang Y; Daugherty CJ; Morton CC; Zhou F; Campos-Torres J; Leder P

Abstract: We have generated a mouse model for ataxia-telangiectasia 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 ataxia-telangiectasia 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 both of these can lead to the development of the disease.

Keywords: Animals; Ataxia Telangiectasia/*genetics; Cell Cycle Proteins; Cells, Cultured; Chimera; Crosses, Genetic; DNA-Binding Proteins; Embryo, Mammalian; Exons; Female; Fibroblasts; Genotype; Heterozygote Detection; Homozygote; Humans; Karyotyping; Leucine Zippers; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Protein Biosynthesis; *Protein-Serine-Threonine Kinases; Proteins/*genetics; Seminiferous Tubules/pathology; Spleen/immunology; T-Lymphocytes/immunology; Thymus Gland/immunology; Tumor Suppressor Proteins
Journal: Proceedings of the National Academy of Sciences of the United States of America
Volume: 93
Issue: 23
Pages: 13084-9
Date: Nov. 12, 1996
PMID: 8917548
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Citation:

Elson A, Wang Y, Daugherty CJ, Morton CC, Zhou F, Campos-Torres J, Leder P (1996) Pleiotropic defects in ataxia-telangiectasia protein-deficient mice. Proceedings of the National Academy of Sciences of the United States of America 93: 13084-9.


Study Lifespan Factors:
  • Atm Ataxia telangiectasia mutated homolog (human)


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