| Project/Area Number |
17590957
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Endocrinology
|
|---|
| Research Institution | Shinshu University |
|---|
Principal Investigator |
HASHIZUME Kiyoshi Shinshu University, Graduate School of Medicine, Department of Aging medicine and Geriatrics, Professor, 大学院・医学研究科, 教授 (60092889)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Satoru Shinshu Univeristy, Graduate School of Medicine, Department of Aging medicine and Geriatrics, Assisstant, 大学院・医学研究科, 助手 (30222061)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥2,500,000 (Direct Cost: ¥2,500,000)
|
|---|
| Keywords | thyroid hormone / CRYM / mu-crystallin / ABR / NADPH / knockout mouse / 3,5,3'-triiodo-L-thyronine |
|---|
| Research Abstract |
Previously, we identified NADPH-dependent cytosolic T3 binding protein (CTBP) in rat cytosol. CTBP is identical to m-crystallin (CRYM). Recently, CRYM mutations were found in patients with non-syndromic hereditary deafness. Although it has been established that CRYM plays pivotal roles in reserving and transporting T3 into the nuclei in vitro and has a clinical impact on hearing ability, the precise functions of CRYM remain to be elucidated in vivo.
To further investigate the in vivo functions of CRYM gene products, we have generated mice with targeted disruption of the CRYM gene, which abrogates the production of CRYM. CRYM knockout loses the NADPH-dependent T3 binding activity in the cytosol of the brain, kidney, heart, and liver. At the euthyroid state, knockout significantly suppresses the serum concentration of T3 and T4 despite normal growth, heart rate and hearing ability. The disruption of the gene does not alter the expression of TSHb mRNA in the pituitary gland or glutathione S transferase alpha 2 and deiodinase 1 mRNAs in either the liver or kidney. When radiolabeled T3 is injected intravenously, labeled T3 rapidly enters into then escapes from the tissues in CRYM-knockout mice. These data suggest that because of rapid T3 turnover, disruption of the CRYM gene decreases T3 concentrations in tissues and serum without alteration of peripheral T3 action in vivo.
|
