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

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

Research output: Contribution to journalArticle

91 Citations (Scopus)

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

Fingerprint

Azoospermia
Transgenes
Phenotype
Germ Cells
Genes
Primates
Pachytene Stage
Yeast Artificial Chromosomes
Oligospermia
Seminiferous Tubules
Chromosomes, Human, Pair 3
RNA-Binding Proteins
Sertoli Cells
Meiosis
Spermatogenesis
Multigene Family
Contraceptive Agents
Testis
Up-Regulation
Survival

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

A human DAZ transgene confers partial rescue of the mouse Dazl null phenotype. / Slee, R.; Grimes, Brenda; Speed, R. M.; Taggart, M.; Maguire, S. M.; Ross, A.; McGill, N. I.; Saunders, P. T K; Cooke, H. J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 96, No. 14, 06.07.1999, p. 8040-8045.

Research output: Contribution to journalArticle

Slee, R. ; Grimes, Brenda ; Speed, R. M. ; Taggart, M. ; Maguire, S. M. ; Ross, A. ; McGill, N. I. ; Saunders, P. T K ; Cooke, H. J. / A human DAZ transgene confers partial rescue of the mouse Dazl null phenotype. In: Proceedings of the National Academy of Sciences of the United States of America. 1999 ; Vol. 96, No. 14. pp. 8040-8045.
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