THE MOUSE Y-CHROMOSOME INTERVAL NECESSARY FOR SPERMATOGONIAL PROLIFERATION IS GENE DENSE WITH SYNTENIC HOMOLOGY TO THE HUMAN AZFA REGION

The Delta Sxr(b) deletion interval of the mouse Y chromosome contains Spy, a spermatogenesis factor gene(s) whose expression is essential fo r the postnatal development: of the mitotic germ cells, spermatogonia, The boundaries of Delta Sxr(b) are defined by the duplicated genes Zf y1 and Zfy2 and four further genes have previously been mapped within the interval: Ube1y and Smcy linked with Zfy1 on a contig of 250 kb, a nd Dffry and Uty,which were unanchored, The interval was estimated to be >450 kb. In order to identify any further gene(s) that may underlie Spy,systematic exon trapping was performed on an extended contig, anc hored on Zfy1, which covers 750 kb of the Delta Sxr(b) interval. Exons from two novel genes were isolated and placed together with Dffry and Uty on the contig in the order Dffry-Dby-Uty-Tspy-Eif2 gamma y-Smcy-U be1y-Zfy1. All the genes, with the double exception of Tspy, are X-Y h omologous and produce putatively functional, spliced transcripts. The tight linkage and order of Dffry, Dby and Uty was shown to be conserve d in deletion intervals 5C/5D of the human Y chromosome by the constru ction of a contig of human PAC and YAC clones; this represents the fir st example of syntenic homology between Y chromosomes from two distinc t mammalian orders. Interval 5C/5D contains the distal boundary of the AZFa interval, which, like Delta Sxr(b) is believed to be necessary f or spermatogonial development in the prepubertal testis, Our results t herefore show that AZFa and Spy may be encoded by homologous genes.