| Project/Area Number |
17590843
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Kidney internal medicine
|
|---|
| Research Institution | Kyoritsu University of Pharmacy |
|---|
Principal Investigator |
HOSOYAMADA Makoto Kyoritsu University of Pharmacy, Pharmacy, Associate Professor (00291659)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ICHIDA Kimiyoshi Tokyo University of Pharmacy, Pharmacy, Professor (80183169)
MORISAKI Takayuki National Circulation Reseach Center, Bioscience, Professor (30174410)
|
|---|
| Project Period (FY) |
2005 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
|
| Budget Amount *help |
¥3,710,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
|---|
| Keywords | Urate / Transporter / Knockout mice |
|---|
| Research Abstract |
Mouse ES cell was transformed with the targeting vector which was constructed by insertion of Neomycin resistance gene (pMC1Neo-polyA) and Diphtheria toxin A gene (pSK-DTA) into 〜15kb mouse URAT1 gene (Slc22a12) cloned from a genomic DNA phagemid library: Homologus recombinant ES cell clone was selected by Neomycin and verified by PCR and genomic southern blotting, and injected into blastcyst to get chimera mouse. Homozygous mouse was established by mating of heterozygous Fl mice which were derived from the chimera mice and wild C57BL/6. As the phenotype of homozygous mice, there is no anomaly by naked eye observation, and no renal expression of URAT1 was confirmed by RT-PCR and Western blotting.
Daily urine volumes were increased in homozygous mice. There in no significance in serum creatinine concentrations. Serum urate concentrations in wild mice were significantly increased in oxonate-treated group higher than control group, however, those in homozygous mice have no significance between oxonate-treated group and control group. Daily amounts of urinary creatinine excretions were increased in both homozygous groups. Daily amounts of urinary urate excretions in wild mice were significantly increased in oxonate-treated group higher than control group, however, those in homozygous mice have no significance between oxonate; treated group and control group. There in no significance in serum creatinine clearances. Fractional excretion of urate (FEua) in wild mice were significantly decreased in oxonate-treated group lower than control group, however, those in homozygous mice have no significance between oxonate-treated group and control group.
|
