| Project/Area Number |
11670754
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Pediatrics
|
|---|
| Research Institution | Gifu University |
|---|
Principal Investigator |
FUKAO Toshiyuki Gifu University School of Medicine, Research Associate, 医学部・附属病院, 助手 (70260578)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
INOUE Ryosuke Gifu University School of Medicine, Research Associate, 医学部・附属病院, 助手 (60273132)
SUKEGAWA Kazuko Gifu University School of Medicine, Research Associate, 医学部, 助手 (60115409)
|
|---|
| Project Period (FY) |
1999 – 2000
|
| Project Status |
Completed (Fiscal Year 2000)
|
| Budget Amount *help |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
|
|---|
| Keywords | beta-ketothiolase deficiency / mitochondrial acetoacetyl-CoA thiolase / succinyl-CoA : 3-ketoacid CoA transferase / gene cloning / gene mutation / gene regulation / ketone body / ミトコンドリア・アセトアセチル-CoAチオラーゼ / T2欠損症 / サクシニル-CoA:3ケト酸CoAトランスフェラーゼ / サクシニル-CoA:3ケト酸CoAトランスフェラーゼ欠損症 / ミトコンドリア.アセトアセチル-CoAテオラーゼ |
|---|
| Research Abstract |
1) SCOT deficieicny : We revealed the structure and sequence of human SCOT gene, made tertiary structural model of human SCOT protein, and identified and characterized gene mutations in 3 SCOT deficient patients. We now can screen SCOT gene mutations at the genomic level. We analyzed 5' flanking regions of human SCOT gene in order to clarify the mechanism for specific SCOT gene supression in hepatocytes. We determined the sequence of 3 kb in the region, and revealed that Sp1 basically drive the SCOT gene expression. We also searched cis-elements responsible for specific supression in hepatocytes.
2) T2 deficiency : We analyzed character of amino acid alternations (gene mutations) identified in 5 spanish T2 deficient patients on teritiary structural model of T2 protein. In one patient, we identified a novel splicing mutation 380C>T.This mutation located on exon 3 activated pre-exsisting cryptic splice site on exon 3, resulting in exclusive splicing at the cryptic site. We have identified gene mutations in 26 T2 deficient patients. We collected clinical information from the physicians for these patients with the use of questionnaire to search clinical courses and outcome and to clarifiy genotype/phenotype correlation in T2 deficiency. By the study, we concluded that (1) T2 deficiency has a favorable outcome in general ; (2) severe ketoacidotic attack can be avoidable after confirmation of the diagnosis ; (3) there is no apparent phenotype/genotype correlation.
The head investigator was honored to write chapters in "Methods in Enzymology" and in "Metabolic ＆ Molecular Bases of Inherited Disease".
|
