| First Author | Huang CY | Year | 2007 |
| Journal | J Exp Med | Volume | 204 |
| Issue | 6 | Pages | 1371-81 |
| PubMed ID | 17502661 | Mgi Jnum | J:125881 |
| Mgi Id | MGI:3760069 | Doi | 10.1084/jem.20061460 |
| Citation | Huang CY, et al. (2007) Defects in coding joint formation in vivo in developing ATM-deficient B and T lymphocytes. J Exp Med 204(6):1371-81 |
| abstractText | Ataxia-telangiectasia mutated (ATM)-deficient lymphocytes exhibit defects in coding joint formation during V(D)J recombination in vitro. Similar defects in vivo should affect both T and B cell development, yet the lymphoid phenotypes of ATM deficiency are more pronounced in the T cell compartment. In this regard, ATM-deficient mice exhibit a preferential T lymphopenia and have an increased incidence of nontransformed and transformed T cells with T cell receptor alpha/delta locus translocations. We demonstrate that there is an increase in the accumulation of unrepaired coding ends during different steps of antigen receptor gene assembly at both the immunoglobulin and T cell receptor loci in developing ATM-deficient B and T lymphocytes. Furthermore, we show that the frequency of ATM-deficient alphabeta T cells with translocations involving the T cell receptor alpha/delta locus is directly related to the number of T cell receptor alpha rearrangements that these cells can make during development. Collectively, these findings demonstrate that ATM deficiency leads to broad defects in coding joint formation in developing B and T lymphocytes in vivo, and they provide a potential molecular explanation as to why the developmental impact of these defects could be more pronounced in the T cell compartment. |
