1990 Fiscal Year Final Research Report Summary
Molecular Genetic Study of Mouse Senile Amyloidosis
| Project/Area Number |
01570190
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Kuoto University |
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Principal Investigator |
HIGUCHI Keiichi Chest Disease Research Institute, Kyoto University. Lecturer, 胸部疾患研究所 講師 (20173156)
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| Co-Investigator(Kenkyū-buntansha) |
HOSOKAWA Masanori Chest Disease Research Institute, Kyoto University. Associate Professor, 胸部疾患研究所, 助教授 (00127135)
TAKEDA Toshio Chest Disease Research Institute, Kyoto University. Professor, 胸部疾患研究所, 教授 (00027088)
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| Project Period (FY) |
1989 – 1990
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| Keywords | Senile Amyloidosis / Mouse / apoA-II / Senescence Accelerated Mouse (SAM) / PCR / RFLP / Genetic Study / mRNA |
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| Research Abstract |
The apoA-II gene was amplified by polymerase chain reaction (PCR) from chromosomal DNA of nine inbred strains of mice. Sequence analysis of the PCR products indicated the presence of three types of apoA-II genes. Three types of apoA-II proteins (A, B and C) were predicted from the nucleotide sequence of apoA-II cDNA. Substitution of amino acid residues was noted at 4 positions. Each type was identifiable by digestion of PCR amplified apoA-II DNA, using restriction enzyme Cfr13I and MspI. The mouse strains, SAM-P/1, SAM-P/2, SJL/J, A/J had type A apoA-II. These strains generally exhibit amyloid deposition from relatively younger age. Examination of types of apoA-II and amyloid deposition in the F2 hybrid mice showed that apoA-II amyloid deposition was present only in the homozygous mice for type A apoA-II. We postulate that the molecular structure of apoA-II may be an important factor involved in the development of senile amyloidosis in mice.
The expression levels of apoA-II mRNA in the liver of the SAM-P/1 strains of mice decreased rapidly with advancing age. The expression levels of apoA-II mRNA at the age of 14 months was 50 % of the level at the age of 2 months.
The new system was developed for determination of amyloid fibrils specifically and kinetics of amyloid fibril polymerization was analyzed.
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