Concomitant loss of proapoptotic BH3-only Bcl-2 antagonists Bik and Bim arrests spermatogenesis

Leigh Coultas, Philippe Bouillet, Kate L. Loveland, Sarah Meachem, Harris Perlman, Jerry M. Adams*, Andreas Strasser

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

The BH3-only proteins of the Bcl-2 family initiate apoptosis through the activation of Bax-like relatives. Loss of individual BH3-only proteins can lead either to no phenotype, as in mice lacking Bik, or to marked cell excess, as in the hematopoietic compartment of animals lacking Bim. To investigate whether functional redundancy with Bim might obscure a significant role for Bik, we generated mice lacking both genes. The hematopoietic compartments of bik -/-bim-/- and bim-/- mice were indistinguishable. However, although testes develop normally in mice lacking either Bik or Bim, adult bik-/-bim-/- males were infertile, with reduced testicular cellularity and no spermatozoa. The testis of young bik-/-bim-/- males, like those lacking Bax, exhibited increased numbers of spermatogonia and spermatocytes, although loss of Bik plus Bim blocked spermatogenesis somewhat later than Bax deficiency. The initial excess of early germ cells suggests that spermatogenesis fails because supporting Sertoli cells are overwhelmed. Thus, Bik and Bim share, upstream of Bax, the role of eliminating supernumerary germ cells during the first wave of spermatogenesis, a process vital for normal testicular development.

Original languageEnglish (US)
Pages (from-to)3963-3973
Number of pages11
JournalEMBO Journal
Volume24
Issue number22
DOIs
StatePublished - Nov 16 2005

Keywords

  • Apoptosis
  • BH3-only protein
  • Bik
  • Bim
  • Spermatogenesis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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