Targeted disruption of intracellular type I platelet activating factor-acetylhydrolase catalytic subunits causes severe impairment in spermatogenesis

Hiroyuki Koizumi, Noritaka Yamaguchi, Mitsuharu Hattori, Tomo O. Ishikawa, Junken Aoki, Makoto M. Taketo, Keizo Inoue, Hiroyuki Arai

Research output: Contribution to journalArticlepeer-review

68 Citations (Scopus)

Abstract

Intracellular type I platelet activating factor-acetylhydrolase is a phospholipase that consists of a dimer of two homologous catalytic subunits α1 and α2 as well as LIS1, a product of the causative gene for type I lissencephaly. LIS1 plays an important role in neuronal migration during brain development, but the in vivo function of the catalytic subunits remains unclear. In this study, we generated αl- and α2-deficient mice by targeted disruption. α-/- mice are indistinguishable from wild-type mice, whereas α2-/- male mice show a significant reduction in testis size. Double-mutant male mice are sterile because of severe impairment of spermatogenesis. Histological examination revealed marked degeneration at the spermatocyte stage and an increase of apoptotic cells in the seminiferous tubules. The catalytic subunits are expressed at high levels in testis as well as brain in mice. In wild-type mice, α2 is expressed in all seminiferous tubule cell types, whereas al is expressed only in the spermatogonia. This expression pattern parallels the finding that deletion of both subunits induces a marked loss of germ cells at an early spermatogenic stage. We also found that the LIS1 protein levels, but not the mRNA levels, were significantly reduced in α2-/- and double-mutant mice, suggesting that the catalytic subunits, especially α2, are a determinant of LIS1 expression level.

Original languageEnglish
Pages (from-to)12489-12494
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number14
DOIs
Publication statusPublished - 2003 Apr 4

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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