MAPPING A GENE FOR COMBINED HYPERLIPIDEMIA IN A MUTANT MOUSE STRAIN

Familiar combined hyperlipidaemia (FCHL) is a common, multifactorial d isorder associated with elevated levels of plasma triglyceride, choles terol, or both(1-3). A characteristic feature is increased secretion o f very low density lipoproteins (VLDL) and apolipoprotein B (apoB; ref s 3,4). Although FCHL is the most common cause of premature coronary a rtery disease (CAD), accounting for over 10% of cases, its aetiology r emains largely unknown(3-6). One powerful approach to the dissection o f complex genetic traits involves the use of animal models' We have id entified a mouse strain, HcB-19/Dem (HcB-19), which exhibits hypertrig lyceridaemia, hypercholesterolaemia and elevated levels of plasma apoB . Like FCHL patients, HcB-19 mice also exhibit increased secretion of triglyceride-rich lipoproteins, and their hyperlipidaemia becomes prog ressively more severe with age. It is likely that the hyperlipidaemia results from a mutation of a novel gene that arose during development of strain HcB-19. We mapped the hyperlipidaemia gene (Hyplip1) to the distal portion of mouse chromosome 3. This region is syntenic to human chromosome 1q21-q23, which has recently been shown to harbour a gene associated with FCHL in families from a Finnish isolate (see accompany ing manuscript by Pajukanta et al., ref. 8).