title: Brca2 deficiency leads to T cell loss and immune dysfunction.
abstract: 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 naïve 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.
authors: Department of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742, Korea.
authors: Jun-Hyeon
authors: JH
authors: Jeong
authors: Samsung Genome Institute, Samsung Medical Center, Seoul 135-710, Korea.|SAIHST, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea.
authors: Areum
authors: A
authors: Jo
authors: Department of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742, Korea.
authors: Pilgu
authors: P
authors: Park
authors: Department of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742, Korea.
authors: Hyunsook
authors: H
authors: Lee
authors: Samsung Genome Institute, Samsung Medical Center, Seoul 135-710, Korea.|SAIHST, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea.
authors: Hae-Ock
authors: HO
authors: Lee
mesh_terms: D000818:Animals; D024682:BRCA2 Protein / Q000172:deficiency / Q000235:genetics*; D001483:Base Sequence; D005199:Fanconi Anemia / Q000235:genetics / Q000276:immunology; D007111:Immunity, Cellular; D008822:Mice, Transgenic; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D024682:BRCA2 Protein; C106711:BRCA2 protein, mouse; D016159:Tumor Suppressor Protein p53
keywords: T cell; breast cancer type 2 susceptibility gene (BRCA2); knockout mouse