A deletion of the paracellin-1 gene is responsible for renal tubular dysplasia in cattle

Various hereditary diseases analogous to particular human heritable disease s have been identified in cattle, Investigation of these cattle diseases wi ll provide useful information regarding the pathogenesis of the correspondi ng human diseases. Renal tubular dysplasia is an autosomal recessive diseas e of Japanese black cattle characterized by renal failure and growth retard ation. We have previously mapped the locus responsible for the disease with in a region on bovine chromosome 1. Tn the present study, we further typed additional markers in this region and found that a genomic segment of bovin e chromosome 1 including the microsatellite marker BMS4009 was deleted in t he affected animals. Construction of a physical map covering this region wi th BAC clones and comparison of the nucleotide sequences of this region bet ween normal and affected animals revealed that a region of 37 kb including exons 1 to 4 of the bovine paracellin-1 gene was deleted in the: affected a nimals. The paracellin-1 gene, which is the causative gene for human renal hypomagnesemia with hypercaciuria and nephrocalcinosis, encodes a tight jun ction protein of renal epithelial cells. Therefore, we concluded that delet ion of the paracellin-1 gene is responsible for renal tubular dysplasia of cattle, and the cattle disease could be a good model for the human disease. (C) 2000 Academic Press.