MOUSE HOMOLOGS OF THE HUMAN AZF CANDIDATE GENE RBM ARE EXPRESSED IN SPERMATOGONIA AND SPERMATIDS, AND MAP TO A Y-CHROMOSOME DELETION INTERVAL ASSOCIATED WITH A HIGH-INCIDENCE OF SPERM ABNORMALITIES

An RNA-binding motif (RBM) gene family has been identified on the huma n Y chromosome that maps to the same deletion interval as the 'azoospe rmia factor' (AZF), We have identified the homologous gene family (Rbm ) on the mouse Y with a view to investigating the proposal that this g ene family plays a role in spermatogenesis. At least 25 and probably > 50 copies of Rbm are present on the mouse Y chromosome short arm locat ed between Sry and the centromere. As in the human, a role in spermato genesis is indicated by a germ cell-specific pattern of expression in the testis, but there are distinct differences in the pattern of expre ssion between the two species, Mice carrying the deletion Y-d1, that m aps to the proximal Y short arm, are female due to a position effect r esulting in non-expression of Sry; sex-reversing such mice with an Sry transgene produces males with a high incidence of abnormal sperm, mak ing this the third deletion interval on the mouse Y that affects some aspect of spermatogenesis, Most of the copies of Rbm map to this delet ion interval, and the Y-d1 males have markedly reduced Rbm expression, suggesting that RBM deficiency may be responsible for, or contribute to, the abnormal sperm development, In man, deletion of the functional copies of RBM is associated with meiotic arrest rather than sperm ano malies; however, the different effects of deletion are consistent with the differences in expression between the two species.