2007 Fiscal Year Final Research Report Summary
Identification of a susceptible gene for the development of nephritis, which locates near the D8 GOT128 marker in rat chromosome 8
| Project/Area Number |
18500331
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Laboratory animal science
|
|---|
| Research Institution | Showa University |
|---|
Principal Investigator |
MORITA Hiroyuki Showa University, Department of Medicine, Associate Professor (00311994)
|
|---|
| Project Period (FY) |
2006 – 2007
|
| Keywords | experimental nephritis / focal segmental glomerulosclerosis (FSGS) / nephritis / susceptibility gene / SNP / proteinuria |
|---|
| Research Abstract |
Focal and segmental glomerulosclerosis (FSGS) is a frequent finding in the progression of chronic renal failure. We identified a FSGS susceptibility gene in the BUF/Mna rat, which locate on rat chromosome 13. In the [(BUF/Mna x WKY/NCrj)F1 x BUF/Mna] backcross rats, we found that there was a modifier gene on rat chromosome 8 and 9. The purpose of the present study is to identify the gene on rat chromosome 8. In the F2 backcross cohort, urinary protein excretion increased in those individuals who showed BUF/Mna homozygousity for the D8Mit5 and ACPH markers. Using the NCBI data base UniSTS site, DNA markers were picked up. Some of them showed length polymorphism between BUF/Mna and WKY/NCrj strains and were used in typing. The results of the typing, together with gene information obtained from Ensemble data base, led us construct a physical map that indicated a candidate region on rat chromosome 8 (81.6-86.6 Mb). There were 30 genes in the region. PCR direct sequencing was performed, and then coding sequence of these genes were determined in the BUF/Mna and WKY/NCrj strains. A point mutation, which results in leucine-prolin substitution, was found in interphotoreceptor matrix proteoglycan 1 (Impg1) gene. Specific antibodies were produced by the use of DNA synthesis method. However, the antibodies were not capable of staining rat tissues and organs. (Lama1 is a modifier gene candidate on rat chromosome 9. Immunohistochemical analysis clearly showed that Lamal is expressed in tubular basement membranes of the kidney.)
|
Research Products
(19 results)
