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KMID : 0578320150380030251
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Molecules and Cells
2015 Volume.38 No. 3 p.251 ~ p.258
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Brca2 Deficiency Leads to T Cell Loss and Immune Dysfunction
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Jeong Jun-Hyeon
Jo A-Reum
Park Pil-Gu
Lee Hyun-Sook
Lee Hae-Ock
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Abstract
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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 na?ve 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.
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KEYWORD
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breast cancer type 2 susceptibility gene (BRCA2), knockout mouse, T cell
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