Mapping a gene for combined hyperlipidaemia in a mutant mouse strain

Nat Genet. 1998 Apr;18(4):374-7. doi: 10.1038/ng0498-374.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age Factors
  • Animals
  • Cholesterol / blood
  • Cholesterol, HDL / blood
  • Cholesterol, VLDL / blood
  • Chromosome Mapping
  • Chromosomes / genetics
  • Chromosomes, Human, Pair 1 / genetics
  • Female
  • Genes / genetics*
  • Genetic Linkage
  • Humans
  • Hyperlipidemias / genetics*
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Mutant Strains / genetics*
  • Microsatellite Repeats / genetics
  • Species Specificity
  • Triglycerides / blood


  • Cholesterol, HDL
  • Cholesterol, VLDL
  • Triglycerides
  • Cholesterol