A genetic locus susceptible to the overt proteinuria in BUF/Mna rat

The BUF/Mna (BUF) strain is a high-proteinuria line of rats, and virtually all rats develop overt proteinuria by the age of 20 weeks. Genetic analysis revealed that proteinuria susceptibility was determined principally by two autosomal recessive genes. These findings prompted us to perform genetic mapping of the genes. (BUF/Mna x WKY/NCrj) F1 x BUF/Mna backcross rats were raised and maintained for 40-60 weeks to detect proteinuria. DNAs were extracted from ears of these rats and were examined by linkage study with polymerase chain reaction (PCR) with 132 microsatellite markers. Fifty-three out of 167 rats developed proteinuria. DNAs of 51 out of these 53 rats showed homozygous BUF/BUF genotype in the D13Mgh4 and D13N1 markers located on Chromosome (Chr) 13. The D13Rat1, D13Mgh2, D13Rat13, D13Mgh3, Syt2, Ren, D13Rat25, D13Mit2, D13Mgh5, and D13N2 markers located on the chromosome also showed statistically significant linkage to the development of proteinuria, whereas the other 110 markers showed no linkage. Here we report that a proteinuria-susceptible gene, Pur1, resides on a region flanked by the loci D13Mgh3 and D13Mgh4 on Chr 13.