| Project/Area Number |
06454172
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | The Institute of Physical & Chemical Research (RIKEN) |
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Principal Investigator |
ISHII Shunsuke The Institute of Physical & Chemical Research (RIKEN), Lab.of Molecular Genetics, Lab.Head, 分子遺伝学研究室, 主任研究員 (00124785)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1995: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1994: ¥3,800,000 (Direct Cost: ¥3,800,000)
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| Keywords | transcription factors / mutant mice / physiological function / 変異マウス |
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| Research Abstract |
In this research, the mutant mice lacking the gene encoding various CRE (cAMP response element)-binding proteins described below were made and the observed abnormalities were analyzed from various aspects.
So far, more than 10 CRE-binding proteins were identified by cDNA cloning. These proteins can be divided into two types ; one is CREB type which is directly phosphorylated by PKA,and another is CRE-BP1 (also called ATF-2) which is phosphorylated with Jun kinase of the stress-activated kinases. Since CRE-BP1 forms a heterodimer with c-Jun, it is important for a cross-talk between PKA and PKC pathways. CRE-BP1 family contains other two members, CRE-BPa and ATF-a. We have made three kinds of mutant mice lacking CRE-BP1, CRE-BPa, or ATF-a genes using the gene knock out technique. All of heterozygotes appears to be normal, but the abnormalities were observed in all of the homozygotes. The CRE-BP1 deficient homozygotes died within 20-30 min after birth. No obvious histological abnormalities were found in all tissues, suggesting that an abnormal signal transduction in the neuronal cells is caused by deficiency of CRE-BP1 activity which destroys the noram function of central nervous system. The CRE-BPa-deficient homozygotes are embryonic lethal. The ATF-a deficiency appears to cause the male-specific embryonic lethality. These results indicate that each of three members of the CRE-BP1 gene family have their own physiological role.
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