Arrested spermatogenesis and evidence for DNA damage in PTIP mutant testes.
The differentiation of mature sperm from male germ cells requires both chromatin remodeling and compaction as well as DNA double stranded break repair of sister chromatids. We examined the function of PTIP, a protein implicated in both DNA repair and histone methylation, during spermatogenesis by using a conditional, inducible mutation in adult male mice. Loss of PTIP led to the developmental arrest of spermatocytes, testicular atrophy, and infertility. By immunostaining with specific markers for different stages of spermatogenesis and for proteins involved in DNA damage and repair mechanisms, we conclude that the lack of PTIP results in genomic instability and DNA damage resulting in the cessation of spermatogenesis in meiosis I. These data underscore the importance of PTIP in the DNA repair process associated with the development of mature spermatozoa.
Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
Kristopher R
KR
Schwab
Gary D
GD
Smith
Gregory R
GR
Dressler
D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins; D020869:Gene Expression Profiling; D042822:Genomic Instability / Q000235:genetics*; D008297:Male; D008540:Meiosis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000235:genetics*; D013091:Spermatogenesis / Q000235:genetics*; D013737:Testis / Q000378:metabolism*; D013739:Testosterone / Q000097:blood
D002352:Carrier Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C412792:Paxip1 protein, mouse; D013739:Testosterone