title: Mice with Y chromosome deletion and reduced Rbm genes on a heterozygous Dazl1 null background mimic a human azoospermic factor phenotype.
abstract: A subset of azoospermia or oligozoospermia patients have microdeletions in defined regions of their Y chromosome, namely the AZFa, b, and c regions. Candidate genes in humans that may cause the azoospermia factor (AZF) phenotype have been assigned to these regions and can include the DAZ and RBM genes. Part of the variability in the AZFc phenotype might be due to interaction between the effects of deleting the DAZ and RBM genes. We mimicked human deletions of RBM and DAZ in the mouse by crossing male mice with a deleted Y chromosome with a reduced number of Rbm genes (Y(d1)) to heterozygote Dazl1 null female mice to study the interaction of the Dazl1 and Rbm or other genes located in the Y(d1) deletion interval. Dazl-/+ Y(d1) animals showed a significant reduction in the sperm count (P < 0.001), an increase of abnormal sperm heads and prominent mid-piece defects of the tails compared to either mutation alone (P < 0.001). Hence, Dazl1 and the genes removed on the Y(d1) chromosome are active in different pathways contributing to different stages of spermatogenesis. Reduction of Dazl1 and Rbm genes as well as/or deletion of the Y chromosome in mice gives rise to a phenotype similar to the heterogeneous AZFc phenotype observed in humans.
authors.affiliation: MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh EH4 2XU, UK.
authors.forename: T
authors.initials: T
authors.lastname: Vogel
authors.forename: R M
authors.initials: RM
authors.lastname: Speed
authors.forename: P
authors.initials: P
authors.lastname: Teague
authors.forename: H J
authors.initials: HJ
authors.lastname: Cooke
mesh_terms: D000818:Animals; D000075364:Deleted in Azoospermia 1 Protein; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D008297:Male; D051379:Mice; D009687:Nuclear Proteins; D009845:Oligospermia / Q000235:genetics*; D010641:Phenotype; D016601:RNA-Binding Proteins / Q000235:genetics*; D013076:Sperm Count; D013077:Sperm Head / Q000648:ultrastructure; D013082:Sperm Tail / Q000648:ultrastructure; D014998:Y Chromosome
chemical_list: C095668:DAZ1 protein, human; D000075364:Deleted in Azoospermia 1 Protein; D009687:Nuclear Proteins; C501499:RBMY1A1 protein, human; D016601:RNA-Binding Proteins; C501500:Rbmy protein, mouse