Polymorphisms of mouse apolipoprotein A-11: seven alleles found among 41 inbred strains of mice

Abstract

In mice, apolipoprotein A-II (apoA-II) associates to form amyloid fibrils in an age-associated manner. We determined the complete nucleotide sequences of the apoA-II gene (Apoa2) cDNA in 41 inbred strains of mice including Mus musculus domesticus (laboratory mouse), Mus musculus castaneus, Mus musculus molossinus, Mus musculus musculus and Mus spretus. Among these strains we identified 7 alleles (Apoa2^a1, Apoa2^a2, Apoa2^b, Apoa2^c, Apoa2^d, Apoa2^e and Apoa2^f). Polymorphisms of nucleotides at 15 positions were detected and amino acid substitutions were found at 8 positions. Apoa2^a1 was found in all mouse subspecies, but Apoa2^b and Apoa2^c were found only in Mus musculus domesticus. Two strains of Mus spretus have the unique alleles Apoa2^eand Apoa2^f which resemble Apoa2^c. We confirmed that VICS in which we found severe amyloidosis here and other amyloidoneic strains in published reports have Apoa2^c allele.

We determined the plasma concentrations of total and HDL cholesterol in the strains of Mus musculus domesticus with the Apoa2^a1, Apoa2^b and Apoa2^c alleles. Significantly higher concentrations of plasma cholesterol were observed in mouse strains with the Apoa2^b allele.

These findings provide fundamental data on mouse Apoa2 alleles. Furthermore, differences in these alleles likely have considerable influence on traits related to amyloidosis and lipid metabolism.

Key Words:

• amyloid protein
• apolipoprotein A-II
• cholesterol
• mouse strains
• polymorphism
• sequence