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Brca2 Deficiency Leads to T Cell Loss and Immune Dysfunction

  • Jeong, Jun-Hyeon (Department of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University) ;
  • Jo, Areum (Samsung Genome Institute, Samsung Medical Center) ;
  • Park, Pilgu (Department of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University) ;
  • Lee, Hyunsook (Department of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University) ;
  • Lee, Hae-Ock (Samsung Genome Institute, Samsung Medical Center)
  • Received : 2014.11.10
  • Accepted : 2014.12.04
  • Published : 2015.03.31

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 na$\ddot{i}$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.

Keywords

breast cancer type 2 susceptibility gene (BRCA2);knockout mouse;T cell

Acknowledgement

Grant : 생명과학 고급인력양성 사업단

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