MOUSE APOLIPOPROTEIN AI - CDNA-DERIVED PRIMARY STRUCTURE, GENE ORGANIZATION AND COMPLETE NUCLEOTIDE-SEQUENCE

Apolipoprotein AI, the dominant protein component of serum high density lipoprotein, is intimately involved in cholesterol homeostasis. Apo AI activates the lecithin-cholesterol acyltransferase within the HDL particle and functions as ligand for a putative HDL receptor - two properties, which render this apolipoprotein a key mediator in reversed cholesterol transport. A functional analysis of the apo AI gene demands the isolation of the mouse apo AI gene for expression as transgenes in different mutant forms in the mouse. Here we describe the isolation of a full length apo AI-specific mouse liver cDNA clone with the human cDNA (892 bp) and the derived amino-acid sequence coding a polypeptide of 264 amino-acid residues. It showed a 70.7% homology to the rat and 66% to the human apo AI sequence. With this cDNA as probe the mouse apo Al gene was isolated and its organization analysed. Four exons, three of which are coding sequences, are aligned similarly to the human gene. The gene embraces 1825 bp between the transcription start, and the poly(A)+ tail attached 62 bp downstream of the stop codon. The complete nucleotide sequence of the four exons and three introns of the mouse apo AI gene was determined and its homology compared with that of the rat and human gene. Extensive deletions and a strongly reduced homology of the three introns of the two genes are obvious.