A human DAZ transgene confers partial rescue of the mouse Dazl null phenotype

R. Slee, B. Grimes, R. M. Speed, M. Taggart, S. M. Maguire, A. Ross, N. I. McGill, P. T.K. Saunders, H. J. Cooke

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Abstract

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

Original languageEnglish (US)
Pages (from-to)8040-8045
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number14
DOIs
StatePublished - Jul 6 1999
Externally publishedYes

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    Slee, R., Grimes, B., Speed, R. M., Taggart, M., Maguire, S. M., Ross, A., McGill, N. I., Saunders, P. T. K., & Cooke, H. J. (1999). A human DAZ transgene confers partial rescue of the mouse Dazl null phenotype. Proceedings of the National Academy of Sciences of the United States of America, 96(14), 8040-8045. https://doi.org/10.1073/pnas.96.14.8040