Evolutionary conservation of the mouse apolipoprotein e-c1-c2 gene cluster: structure and genetic variability in inbred mice.

Abstract

The human apolipoprotein E (APOE), APOC1, pseudo APOC1 (APOC1'), and APOC2 genes are clustered within 48 kb on the long arm of chromosome 19. A mouse Apoe cDNA probe was used to isolate overlapping cosmid clones from a cosmid library of the C57BL/Rij inbred mouse strain. These clones were investigated for the presence of the Apoc1 and Apoc2 genes by heterologous hybridization. Our results show that the Apoe-c1-c2 gene cluster is conserved in the mouse. In line with evolutionary data, the mouse lacks the equivalent of APOC1'. These data were confirmed using a mouse Apoc2 cDNA clone, and surprisingly the cDNA clone isolated here was 965 bp in size, which is on average 450 bp longer than other APOC2 cDNAs described so far. Correspondingly, the Apoc2 gene occupies an unusually large genomic region, due to an extended 5' end. Interestingly, a variable number of tandem repeat (VNTR) in the third intron of the human APOC2 gene shows a high sequence homology and is located at the identical position in the mouse gene. Despite the high copy number of this VNTR (27 or 34 copies) only two variants were found among 11 different inbred strains. With the aid of six restriction fragment length variations in this gene cluster only two different haplotypes could be deduced, indicating that the Apoe-c1-c2 gene cluster is highly conserved in the inbred strains that were studied.