Mapping a gene for combined hyperlipidaemia in a mutant mouse strain.
Familial combined hyperlipidaemia (FCHL) is a common, multifactorial disorder associated with elevated levels of plasma triglyceride, cholesterol, or both. A characteristic feature is increased secretion of very low density lipoproteins (VLDL) and apolipoprotein B (apoB). Although FCHL is the most common cause of premature coronary artery disease (CAD), accounting for over 10% of cases, its aetiology remains largely unknown. One powerful approach to the dissection of complex genetic traits involves the use of animal models. We have identified a mouse strain, HcB-19/Dem (HcB-19), which exhibits hypertriglyceridaemia, 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 progressively 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.
Castellani
L W
LW
Department of Medicine, University of California, Los Angeles 90095, USA.
Weinreb
A
A
Bodnar
J
J
Goto
A M
AM
Doolittle
M
M
Mehrabian
M
M
Demant
P
P
Lusis
A J
AJ
D000367:Age Factors; D000818:Animals; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D002874:Chromosome Mapping; D002875:Chromosomes / Q000235:genetics; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D005260:Female; D005796:Genes / Q000235:genetics*; D008040:Genetic Linkage; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D013045:Species Specificity; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D015243:Cholesterol, VLDL; D014280:Triglycerides; D002784:Cholesterol