POLYMORPHISM OF APOLIPOPROTEIN-A-II (APOA-II) AMONG INBRED STRAINS OF MICE - RELATIONSHIP BETWEEN THE MOLECULAR TYPE OF APOA-II AND MOUSE SENILE AMYLOIDOSIS

Three types of apolipoprotein A-II (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 four positions (type A: Pro-5, Asp-20, Met-26, Ala-38; B: Pro-5, Glu-20, Val-26, Val-38; C: Gln-5, Glu-20, Val-26, Ala-38). Each type was identifiable by digestion of amplified apoA-II DNA by PCR, using restriction-fragment-length polymorphism of the apoA-II gene for restriction enzymes (Cfr13I and MspI. The molecular type of apoA-II was determined among 23 strains of mice including nine of the senescence accelerated mouse series developed in our laboratory. Examination of types of apoA-II and amyloid deposition in the F2 and F3 hybrid mice showed that apoA-II amyloid deposition was present only in the mice homozygous for type C apoA-II and which were 12-17 months of age. The molecular type of apoA-II may be a factor involved in the development of senile amyloidosis in mice.