Spermiogenesis is impaired in mice bearing a targeted mutation in the protein phosphatase 1c gamma gene

Type 1 protein phosphatases (PP1) are involved in diverse cellular activiti es, ranging from glycogen metabolism to chromatin structure modification, m itosis, and meiosis. The holoenzymes are composed of two or more subunits, including a catalytic subunit (PP1c) and one or more regulatory subunits. M any eukaryotes possess several catalytic subunit genes which encode highly conserved isoforms. In rodents, one of these isoforms, PP1c gamma 2, appear s to be expressed predominantly in testes. Whether PP1c gamma 2 performs a testis-specific function is unclear. To address this and other questions, t he PP1c gamma gene was disrupted by targeted insertion in murine embryonic stem cells. Mice derived from these cells were viable, and homozygous femal es were fertile. However, males homozygous for the targeted insertion were infertile. Histological examination revealed severe impairment of spermioge nesis beginning at the round spermatid stage. In addition, defects in meios is were inferred from the presence of polyploid spermatids. Immunohistochem istry revealed the presence of PP1c alpha protein on condensing spermatids in both wild-type and mutant testes, suggesting that this closely related i soform is unable to compensate for the loss of PP1c gamma. These defects ar e discussed in the light of known functions of protein phosphatase 1. (C) 1 999 Academic Press.