Recently, a cDNA (pRS1) was cloned from pig kidney cortex that encodes a membrane-associated protein involved in Na(+)-coupled sugar transport. pRS1 alters sugar transport by SGLT1 from rabbit intestine or by SMIT from dog kidney which is homologous to SGLT1. In contrast, pRS1 does not influence transporters from other genetic families. We report the cloning of the intronless human gene hRS1 (6,743 bp), which encodes a 617-amino-acid protein with 74% amino acid identity to pRS1. By fluorescence in situ hybridization, hRS1 was localized to chromosome 1p36.1. The localization to one chromosome and Southern blot analysis of restricted genomic DNA suggest that there is only one RS1-homologous gene in humans. Functionality of hRS1 was demonstrated by co-expression experiments of hRS1 and SGLT1 from human intestine in oocytes from Xenopus laevis. They show that hRS1-protein inhibits Na(+)-D-glucose co-transport expressed by human SGLT1 by decreasing both the Vmax and the apparent Km value of the transporter. The analysis of the 5'-noncoding sequence of hRS1 revealed different enhancer consensus sequences that are absent in the SGLT1 gene, e.g., several consensus sequences for steroid-binding proteins.

Different Y mutations in Yq11 occurring de novo in sterile males were first described 19 years ago. Since the phenotype of the patients was always associated with azoospermia or severe oligospermia, it was postulated that these mutations interrupt a Y spermatogenesis locus in the euchromatic Y region (Yq11) called azoospermia factor (AZF). Recently, it became possible to map AZF mutations to different subregions in Yq11 by molecular deletion mapping. This indicated that azoospermia is possibly caused by more than one Y gene in Yq11 and the Yq11 chromatin structure. The frequency of AZF mutations in idiopathic sterile males (5-20%) may indicate a need for a general screening programme for its analysis in infertility clinics.

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An experimental approach towards the molecular analysis of the male fertility function, located in interval 6 of the human Y chromosome, is presented. This approach is not based on the knowledge of any gene product but on the assumption that the functional DNA structure of male fertility genes, evolutionary conserved with their position on the Y chromosome, may contain an evolutionary conserved frame structure or at least conserved sequence elements. We tested this hypothesis by using dhMiF1, a fertility gene sequence of the Y chromosome of Drosophila hydei, as a screening probe on a pool of cloned human Y-DNA sequences. We were able to select 10 human Y-DNA sequences of which 7 could be mapped to Y interval 6 (the pY6H sequence family). Since the only fertility gene of the human Y chromosome is mapped to the same Y interval, our working hypothesis seems to be strongly supported. Most interesting in this respect is the isolation of the Y-specific repetitive pY6H65 sequence. The pY6H65 locus extends to a length of at least 300 kb in Y interval 6 and has a locus-specific repetitive sequence organization, reminiscent of the functional DNA structure of Y chromosomal fertility genes of Drosophila. We identified the simple sequence family (CA)n as one sequence element conserved between the Drosophila dhMiFi fertility gene sequence and the homologous human Y-DNA sequences.