2001 Fiscal Year Final Research Report Summary
Studies on the pathophysiological mechanism of myotonic dystrophy
| Project/Area Number |
12670607
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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 |
Neurology
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| Research Institution | Ehime University |
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Principal Investigator |
YAMAGATA Hidehisa Ehime University, Faculty of Medicine, Instructor, 医学部, 助手 (00304618)
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| Co-Investigator(Kenkyū-buntansha) |
MIKI Tetsuro Ehime University, Faculty of Medicine, Professor, 医学部, 教授 (00174003)
KONDO Ikuko Ehime University, Faculty of Medicine, Professor, 医学部, 教授 (20110489)
NOMURA Takuo Ehime University, Faculty of Medicine, Assistant Professor, 医学部, 講師 (20322274)
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| Project Period (FY) |
2000 – 2001
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| Keywords | myotonic dystrophy / (CTG)n repeat / linkage disequilibrium / DNA sequence / multistep model / DMPK protein / gene rearrangement |
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| Research Abstract |
1. DMPK gene haplotype analysis and studies on dynamic mutation
We have collected total of 474 DNA samples ofDM1 family members. Using Southern blot hybridization and PCR methods, we constructed high resolution haplotypes in the DMWD-DMPK-SIX5 region and studied linkage disequilibrium between the markers. As expected, strong linkage disequilibrium was observed when normal alleles were grouped according to CTG repeat length. The data suggested that a major ancient mutation underlying DM1 has originated by reservoir pool (CTG19-37), not by CTG5.
2. Molecular analysis on muscles of congenital myotonic dystrophy patients
We examined autopsied skeletal muscle with 6 severe congenital DM 1 using Southern blot hybridization, Western blot and histochemical studies. Our data indicate that DMPK is expressed even in most severe congenital DM 1 skeletal muscle, and DMPK expression is developmentally regulated even after birth.
3. Functional analysis of DMPK protein
We screnned human heart and skeletal muscle CDNA libraries to search for the proteins which bind to DMPK. Positive clones were Racl and Rho A that belong to myosin binding protein and cytoskeleton.
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