| Project/Area Number |
18591020
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Endocrinology
|
|---|
| Research Institution | Kyoto University |
|---|
Principal Investigator |
TAMUTA Naohisa Kyoto University, Graduate School of Medicine, Assistant Professor (40314207)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
IKEDA Tadashi Kyoto University, Graduate School of Medicine, Associate Professor (40281092)
|
|---|
| Project Period (FY) |
2006 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
|
| Budget Amount *help |
¥3,830,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
|
|---|
| Keywords | Gene / Signal transduction / Cell and Tissue / Circulation and Hypertension / Regulation of Expression / Natriuretic peptide / Isoform / Dominant negative / 受容体 / 遺伝子発現 / 動脈硬化 / 細胞内シグナル伝達 |
|---|
| Research Abstract |
C-type natriureitc peptide (CNP) utilizes guanylyl cyclase (GC) -B as a receptor to inhibit proliferative vascular lesions and to promote endochondral ossification. We have shown that three GC-B isoforms (GC-B1, B2, B3) are generated from the single GC-B gene in mice and that GC-B2 lacking a regulatory region and GC-B3 constituted by an extracellular region only serve as dominant negative isoforms against the CNP-induced increase of intracellular cGMP levels by GC-B1. A reverse transcription and PCR analysis showed that most of GC-B mRNA species in the growth plate cartilage were GC-B1, while expression levels of GC-B2 and GC-B3 are almost equal to the expression level of GC-B1 mRNA in the central nervous system. This observation could explain why the most prominent phenotype of GC-B null mice is dwarfism where the GC-B mRNA level as the sum of three isoforms in the growth plate cartilage is much less than in the cetral nervous system. We investigated if GC-B2 or GC-B3 isoforms were expressed in human tissues, and confirmed that at least GC-B2 isoform is expressed in the human heart Our data indicated that a new GC-B isoform is generated by retaining intron 8, which contains an in-frame stop codon and the isoform is consisted by an extracellular domain, a transmembrane segment, and a short intracellular segment. The expected molecule resembles the molecule generated by a nonsense mutation at GIn500 of human GC-B gene, which causes acromesomelic dysplasia, type Maroteaux.
|
