| Project/Area Number |
11680621
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
MATSUOKA Ichiro Hokkaido University, Grad. Schl. Pharm. Sci., Assoc. Prof., 大学院・薬学研究科, 助教授 (40157269)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | BMP2 / retinoic acid / NT3 / GDNF / sympathetic neuron / BMP / RA-inducible neural-specific protein |
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| Research Abstract |
Roles of bone morphogenetic proteins (BMPs) in the neuronal and glial differentiation have been suggested for both CNS and PNS.We have previously reported the cooperative actions of BMP2 and retinoic acid (RA) in the induction of NT3- and GDNF-responsiveness of developing sympathetic neurons (Mol. Brain Res. 53, 206-217, J.Neurosci. 20, 2917-2925). To analyze further the molecular mechanisms of the synergistic actions of BMP2 and RA, we searched for geneswhose expressions were regulated by BMP2/RA by performing the mRNA differential-display-PCR on cultured embryonic sympathetic neurons. Consequently, we found that several known transcription factor genes as well as novel genes are induced by BMP2/RA in a synergistic manner. As a typical of these genes, BRINP (BMP/RA-inducible neural-specific protein) encodes a novel 88-kDa protein which has no conserved motif. Expression of BRINP as well as its mRNA was restricted to neural cells in both the PNS and CNS, was detected from embryonic period and continues through adulthood, and is upregulated by neural activity. Genomic organization of mouse BRINP gene has been analyzed. The BRINPmRNA expression and promoter activity of BRINP gene upstream region were observed also in several neural cell lines. Interestingly, treatment with NGF increased the promoter activity of BRINP in PC12 cells. We have currently succeeded in producing mice lacking BRINPgene to gain insights on its physiological functions in thedevelopment and functionality of the nervous system.
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