Actin -related protein 3 (Arp3) is mutated in proteinuric BUF/Mna rats
| Autor: | Mutsushi Matsuyama, Kiyoko Nakano, Kiyotaka Akiyama, Shiro Suetsugu, Noriko Wakisaka, Hiroyuki Morita, Seiko Kuraba, Yasuharu Numata, Kiyoko Inui, Hiroaki Oniki, Ashio Yoshimura, Terukuni Ideura, Yoshihisa Yamamoto, Tadaomi Takenawa |
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| Rok vydání: | 2007 |
| Předmět: |
Genetic Markers
Candidate gene Blotting Western Kidney Glomerulus Molecular Sequence Data Quantitative Trait Loci Locus (genetics) Single-nucleotide polymorphism Quantitative trait locus Biology Open Reading Frames Histocompatibility Antigens Genetics Animals Missense mutation SNP Amino Acid Sequence Rats Inbred BUF Genotyping Gene Sequence Analysis DNA Physical Chromosome Mapping Chromosomes Mammalian Molecular biology Actins Protein Structure Tertiary Rats Molecular Weight Proteinuria Gene Expression Regulation Actin-Related Protein 3 Mutation Mutant Proteins Lod Score |
| Zdroj: | Mammalian Genome. 19:41-50 |
| ISSN: | 1432-1777 0938-8990 |
| Popis: | 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 (L)111(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. |
| Databáze: | OpenAIRE |
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