Molecular cloning and nucleotide sequence of cDNA for murine senile amyloid protein: nucleotide substitutions found in apolipoprotein A-II cDNA of senescence accelerated mouse (SAM).
cDNA clones encoding the murine senile amyloid protein (ASSAM) have been isolated from animal models of accelerated senescence (SAM-P/1) and from normal aging (SAM-R/1). Immunochemical and protein sequence studies revealed that apolipoprotein (apo) A-II is a serum precursor of ASSAM. A 17-base synthetic oligonucleotide based on residues 39-44 of ASSAM was used as a hybridization probe for screening newly constructed SAM-P/1 and SAM-R/1 liver cDNA libraries. The structure of murine apo A-II cDNA is of interest because of the amino acid substitution found in ASSAM and serum apo A-II of SAM-P; in SAM-R or other random bred slc:ICR mice, amino acid residue 5 of mature apo A-II is proline but, in SAM-P, this amino acid is changed to glutamine. This amino acid replacement is caused by two nucleotide substitutions (CCA for proline codon to CAG for glutamine codon). The third base mutation may not be relevant to the substitution of amino acid. Attention is directed to the relation of this amino acid substitution to the specific deposition of apo A-II, as a tissue amyloid fibril.