Molecular Genetic Study of Mouse Senile Amyloidosis

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 Cfrl3l and Mspl. 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.