Mice with Y chromosome deletion and reduced Rbm genes on a heterozygous Dazl1 null background mimic a human azoospermic factor phenotype

A subset of azoospermia or oligozoospermia patients have microdeletions in defined regions of their Y chromosome, namely the AZFa, b, and c regions. C andidate genes in humans that may cause the azoospermia factor (AZF) phenot ype have been assigned to these regions and can include the DAZ and RBM gen es. Part of the variability in the AZFc phenotype might be due to interacti on 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 Daz l1 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 abnorm al sperm heads and prominent mid-piece defects of the tails compared to eit her mutation alone (P < 0.001), Hence, Dazl1 and the genes removed on the Y -d1 chromosome are active in different pathways contributing to different s tages of spermatogenesis. Reduction of Dazl1 and Rbm genes as well as/or de letion of the Y chromosome in mice gives rise to a phenotype similar to the heterogeneous AZFc phenotype observed in humans.