Partial rescue of the Dazl knockout mouse by the human DAZL gene.
Y-chromosomal DAZ (deleted in azoospermia) and autosomal DAZ-like (DAZL) comprise a gene family involved in gametogenesis. Y-chromosomal and autosomal genes only co-exist in humans and old world monkeys, indicating that DAZ genes are a recent acquisition of the Y chromosome. In most mammals, the ancestral Dazl alone is sufficient to complete gametogenesis. It is not yet understood why humans and old world monkeys have a second set of genes that are apparently necessary for spermatogenesis, since deletions removing the Y-chromosomal DAZ are often associated with azoo- or oligospermia. We used transgenic mice carrying either human DAZL or human DAZ on a mouse Dazl null background to investigate the functions of the human homologues. Both transgenes enabled prophase spermatocytes to be produced, mainly of the leptonema/zygonema stage, but failed to promote differentiation into mid- to late pachytenes. The presence of human DAZL resulted in a larger amount of early germ cells compared with that observed in DAZ. The degree of rescue was independent of copy number, integration site or presence of the DAZ repeat region for the DAZ transgenes. These findings confirm that DAZL and DAZ can only substitute for early functions of the murine homologue resulting in the establishment of the germ cell population and partial progression into meiosis.
Vogel
T
T
MRC Human Genetics Unit, Western General Hospital, Crewe Rd, Edinburgh EH4 2XU, UK.
Speed
R M
RM
Ross
A
A
Cooke
H J
HJ
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D000075364:Deleted in Azoospermia 1 Protein; D018628:Gene Dosage; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008540:Meiosis; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D012708:Sertoli Cells; D013090:Spermatocytes / Q000166:cytology / Q000502:physiology; D013094:Spermatozoa / Q000166:cytology / Q000502:physiology; D013737:Testis / Q000166:cytology / Q000502:physiology*; D019076:Transgenes / Q000235:genetics*
C095668:DAZ1 protein, human; C101358:DAZL protein, human; D000075364:Deleted in Azoospermia 1 Protein; D011506:Proteins; D016601:RNA-Binding Proteins