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Haploinsufficiency for the murine orthologue of Chlamydomonas PF20 disrupts spermatogenesis.

PF20 was first identified in Chlamydomonas rheinhardtii as an essential component of the axoneme central apparatus. We discovered that the mouse Pf20 gene encodes two major transcripts (2.5 and 1.4 kb), which are expressed in different patterns during spermatogenesis, yielding proteins of 71 and 35 kDa, respectively. Both proteins contain contiguous WD repeats in their C termini. The meiotically expressed 71-kDa protein is incorporated into the central apparatus, whereas the 35-kDa protein, which accumulates in postmeiotic male germ cells, is abundant in the nucleus. We disrupted the Pf20 gene domains that encode the C-terminal WD repeats in embryonic stem cells. Highly chimeric mice carrying the mutant Pf20 allele had impaired spermatogenesis with a significant loss of germ cells at the round spermatid stage, in association with disorganization of sperm axoneme structure. The mutated Pf20 allele was never transmitted, indicating that Pf20 haploinsufficiency caused the defects in spermatogenesis. The 35-kDa PF20 protein was shown to bind to meiosis-expressed gene 1 (MEIG1), a chromosome/chromatin-binding protein initially expressed during meiosis but retained in the germ cell nucleus throughout later stages of spermatogenesis. Our findings reveal an essential role for Pf20 in mouse spermatogenesis, sustaining postmeiotic germ cell viability. The different patterns of expression of the two PF20 proteins suggest the possibility that the Pf20 gene has multiple functions during spermatogenesis.

Pubmed ID: 15328412 RIS Download

Mesh terms: Animals | Cell Cycle Proteins | Cell Nucleus | Chimera | GRB10 Adaptor Protein | Gene Targeting | Gonadal Steroid Hormones | Male | Mice | Microtubule-Associated Proteins | Nuclear Proteins | Phosphoproteins | Protein Isoforms | Proteins | Protozoan Proteins | Spermatogenesis

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Associated grants

  • Agency: NICHD NIH HHS, Id: P01 HD06724
  • Agency: NICHD NIH HHS, Id: R01 HD37416
  • Agency: NICHD NIH HHS, Id: U54 HD028934
  • Agency: NICHD NIH HHS, Id: U54-HD28934
  • Agency: NICHD NIH HHS, Id: R01 HD037416
  • Agency: NIDDK NIH HHS, Id: DK19525
  • Agency: NIDDK NIH HHS, Id: P30 DK019525

Mouse Genome Informatics (Data, Gene Annotation)

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