title: The Magea gene cluster regulates male germ cell apoptosis without affecting the fertility in mice.
abstract: While apoptosis is essential for male germ cell development, improper activation of apoptosis in the testis can affect spermatogenesis and cause reproduction defects. Members of the MAGE-A (melanoma antigen family A) gene family are frequently clustered in mammalian genomes and are exclusively expressed in the testes of normal animals but abnormally activated in a wide variety of cancers. We investigated the potential roles of these genes in spermatogenesis by generating a mouse model with a 210-kb genomic deletion encompassing six members of the Magea gene cluster (Magea1, Magea2, Magea3, Magea5, Magea6 and Magea8). Male mice carrying the deletion displayed smaller testes from 2 months old with a marked increase in apoptotic germ cells in the first wave of spermatogenesis. Furthermore, we found that Magea genes prevented stress-induced spermatogenic apoptosis after N-ethyl-N-nitrosourea (ENU) treatment during the adult stage. Mechanistically, deletion of the Magea gene cluster resulted in a dramatic increase in apoptotic germ cells, predominantly spermatocytes, with activation of p53 and induction of Bax in the testes. These observations demonstrate that the Magea genes are crucial in maintaining normal testicular size and protecting germ cells from excessive apoptosis under genotoxic stress.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, China.
authors.forename: Siyuan
authors.initials: S
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, China.
authors.forename: Li
authors.initials: L
authors.lastname: Xian
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, China.
authors.forename: Peiliang
authors.initials: P
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, China.
authors.forename: Chaojun
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, China.
authors.forename: Zhaoyu
authors.initials: Z
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D005260:Female; D005298:Fertility / Q000502:physiology*; D008297:Male; D058950:Melanoma-Specific Antigens / Q000235:genetics / Q000378:metabolism; D051379:Mice; D005810:Multigene Family / Q000502:physiology*; D013091:Spermatogenesis / Q000502:physiology*; D013094:Spermatozoa / Q000378:metabolism*
chemical_list: D058950:Melanoma-Specific Antigens