First Author | Jeong JH | Year | 2015 |
Journal | Mol Cells | Volume | 38 |
Issue | 3 | Pages | 251-8 |
PubMed ID | 25666348 | Mgi Jnum | J:232670 |
Mgi Id | MGI:5779778 | Doi | 10.14348/molcells.2015.2302 |
Citation | Jeong JH, et al. (2015) Brca2 deficiency leads to T cell loss and immune dysfunction. Mol Cells 38(3):251-8 |
abstractText | Germline mutations in the breast cancer type 2 susceptibility gene (BRCA2) are linked to familial breast cancer and the progressive bone marrow failure syndrome Fanconi anaemia. Established Brca2 mouse knockout models show embryonic lethality, but those with a truncating mutation at the C-terminus survive to birth and develop thymic lymphoma at an early age. To overcome early lethality and investigate the function of BRCA2, we used T cell-specific conditional Brca2 knockout mice, which were previously shown to develop thymic lymphoma at a low penetrance. In the current study we showed that the number of peripheral T cells, particularly naive pools, drastically declined with age. This decline was primarily ascribed to improper peripheral maintenance. Furthermore, heterozygous mice with one wild-type Brca2 allele manifested reduced T cell numbers, suggesting that Brca2 haploinsufficiency might also result in T cell loss. Our study reveals molecular events occurring in Brca2-deficient T cells and suggests that both heterozygous and homozygous Brca2 mutation may lead to dysfunction in T cell populations. |