The BUF/Mna strain of rat is a model of focal and segmental glomerulosclerosis (FSGS) in which a quantitative trait locus
(QTL) for proteinuria,
Pur1, has been identified. The aim of the present study was to identify candidates for the
Pur1 gene. To narrow the
Pur1 QTL, we performed fine QTL mapping and single nucleotide polymorphism (SNP) genotyping. To identify candidate genes, sequencing
and gene-expression analyses of all genes contained in the narrowed locus were conducted. The narrowed
Pur1 region contained 25 genes. Among these genes, only the
Arp3 gene was mutated in the BUF/Mna strain; it contained a missense mutation that caused an
L111
F substitution. This leucine is conserved across species. Gene-expression analysis failed to identify any other candidate genes
for
Pur1. Arp3-mediated actin assembly abnormalities were visible in immunohistochemical and electron microscopic examinations of
podocytes in old BUF/Mna rats. Taken together, these data suggest that
Arp3 is a candidate for the
Pur1 gene. This observation is consistent with our growing recognition that abnormal signaling-induced assembly of actin in podocytes
leads to the development of FSGS.
Nucleotide sequence data reported in this article are available in the DDBJ/EMBL/GenBank database under accession numbers
AB292042-292043 and AB294577-294580.