A HUMAN DAZ TRANSGENE CONFERS PARTIAL RESCUE OF THE MOUSE DAZL NULL PHENOTYPE

作者: R. Slee , B. Grimes , R. M. Speed , M. Taggart , S. M. Maguire

DOI: 10.1073/PNAS.96.14.8040

关键词: TransgeneGerm cellDAZLY chromosomeChromosome 3PopulationBiologyGeneticsGene clusterGene product

摘要: In a subset of infertile men, spectrum spermatogenic defects ranging from complete absence germ cells (sertoli cell only) to oligozoospermia is associated with microdeletions the DAZ (deleted in azoospermia) gene cluster on human distal Yq. encodes testis-specific protein RNA-binding potential recently derived single-copy DAZL1 (DAZ-like) chromosome 3. Y chromosomal homologues are confined humans and higher primates. It remains unclear which function unique primate spermatogenesis may serve, functional status has been questioned. To assess extent conservation we have tested capacity contained 225-kb yeast artificial complement sterile phenotype Dazl null mouse (Dazl−/−), characterized by severe germ-cell depletion meiotic failure. Although Dazl−/− mice remained when transgene was introduced, histological examination revealed partial variable rescue mutant phenotype, manifest as pronounced increase population seminiferous tubules survival pachytene stage meiosis. As well constituting definitive proof role product, these findings confirm high degree between genes, suggesting they constitute single target for contraceptive intervention raising possibility therapeutic up-regulation men.

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