myelin-basic-protein and Ataxia-Telangiectasia

The Atm-/- mice recapitulate most of the defects observed in ataxia-telangiectasia (A-T) patients, including a high incidence of lymphoid tumors and immune defects characterized by defective T cell differentiation, thymus hypoplasia, and defective T-dependent immune responses. To understand the basis of the T cell developmental defects in Atm-/- mice, a functional TCR alpha beta transgene was introduced into these mutant mice. Analysis of the Atm-/-TCR alpha beta+ mice indicated that the transgenic TCR alpha beta can rescue the defective T cell differentiation and partially rescue the thymus hypoplasia in Atm-/- mice, indicating that thymocyte positive selection is normal in the Atm-/- mice. In addition, cell cycle analysis of the thymocytes derived from Atm-/-TCR alpha beta+ and control mice suggested that Atm is involved in the thymocyte expansion. Finally, evaluation of the T-dependent immune responses in Atm-/-TCR alpha beta+ mice indicated that Atm is dispensable for normal T cell function. Therefore, the defective T-dependent immune responses in Atm-/- mice must be secondary to greatly reduced T cell numbers in these mutant mice.

Topics: Animals; Ataxia Telangiectasia; Ataxia Telangiectasia Mutated Proteins; Cell Cycle Proteins; Cell Differentiation; Cell Division; Cells, Cultured; Disease Models, Animal; DNA-Binding Proteins; Lymphocyte Activation; Mice; Mice, Knockout; Mice, Transgenic; Myelin Basic Protein; Peptide Fragments; Protein Serine-Threonine Kinases; Receptors, Antigen, T-Cell, alpha-beta; T-Lymphocytes; Thymus Gland; Transgenes; Tumor Suppressor Proteins