期刊
MOLECULES AND CELLS
卷 38, 期 3, 页码 251-258出版社
KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
DOI: 10.14348/molcells.2015.2302
关键词
breast cancer type 2 susceptibility gene (BRCA2); knockout mouse; T cell
资金
- Basic Science Research Program through the National Research Foundation of Korea - Ministry of Education, Science and Technology [2012-R1A1A3010579, 2011-0018630]
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 hap-loinsufficiency 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.
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