| Project/Area Number |
15K10481
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Orthopaedic surgery
|
|---|
| Research Institution | Nagasaki University |
|---|
Principal Investigator |
KINOSHITA Akira 長崎大学, 原爆後障害医療研究所, 講師 (60372778)
|
|---|
| Co-Investigator(Renkei-kenkyūsha) |
KINOSHITA Naoe 長崎大学, 病院(医学系), 助教 (50380928)
YOSHIURA Koh-Ichiro 長崎大学, 原爆後障害医療研究所, 教授 (00304931)
|
|---|
| Project Period (FY) |
2015-04-01 – 2018-03-31
|
| Project Status |
Completed (Fiscal Year 2017)
|
| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Keywords | カムラチ-エンゲルマン病 / TGF-β1 / iPS細胞 / ゲノム編集 / カムラチ・エンゲルマン病 / 患者iPS細胞 / 骨系統疾患 / カムラチ・エンゲルマン病( / CRISPR/Cas9法 |
|---|
| Outline of Final Research Achievements |
Camurati-Engelmann disease (CAEND) is a rare, autosomal dominant, progressive diaphyseal dysplasia, which is characterized by hyperostosis and sclerosis of the diaphyses of long bones. CAEND is caused by a mutation in the gene TGFB1, encoding TGF-β1. We established induced pluripotent stem (iPS) cells derived from an individual with CAEND. These cells were easier to differentiate than those derived from a healthy individual. Since genetic background strongly affects the CAEND phenotype, we attempted to correct the arginine-to-histidine mutation at residue 218 (R218H) in TGFB1 utilizing a genome editing system. Although we successfully obtained homologous recombinant clones of HEK293T cells, we failed to obtain recombinant clones of iPS cells so far. Furthermore, we discovered new Japanese CAEND cases that had an arginine-to-cysteine mutation at residue 218 in TGFB1. We also identified a de novo mutation in a gene involved in the TGF signaling pathway, which causes hyperostosis.
|
