Ikbkap/Elp1 deficiency causes male infertility by disrupting meiotic progression

PLoS Genet. 2013 May;9(5):e1003516. doi: 10.1371/journal.pgen.1003516. Epub 2013 May 23.

Abstract

Mouse Ikbkap gene encodes IKAP--one of the core subunits of Elongator--and is thought to be involved in transcription. However, the biological function of IKAP, particularly within the context of an animal model, remains poorly characterized. We used a loss-of-function approach in mice to demonstrate that Ikbkap is essential for meiosis during spermatogenesis. Absence of Ikbkap results in defects in synapsis and meiotic recombination, both of which result in increased apoptosis and complete arrest of gametogenesis. In Ikbkap-mutant testes, a few meiotic genes are down-regulated, suggesting IKAP's role in transcriptional regulation. In addition, Ikbkap-mutant testes exhibit defects in wobble uridine tRNA modification, supporting a conserved tRNA modification function from yeast to mammals. Thus, our study not only reveals a novel function of IKAP in meiosis, but also suggests that IKAP contributes to this process partly by exerting its effect on transcription and tRNA modification.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics*
  • Chromosome Pairing / genetics
  • Gene Expression Regulation, Developmental
  • Humans
  • Infertility, Male / genetics*
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Meiosis / genetics*
  • Mice
  • RNA, Transfer / genetics
  • Recombination, Genetic / genetics
  • Spermatogenesis / genetics*

Substances

  • Carrier Proteins
  • Ikbkap protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • RNA, Transfer