Naturally occurring mutations in mice affecting lipid transport and metabolism.

Abstract

Naturally occurring mutations in the mouse provide a unique resource for identifying genes and characterizing proteins involved in lipid metabolism. Spontaneous mouse mutations have been described that affect various aspects of lipid metabolism, including cellular cholesterol homeostasis, fatty acid metabolism, serum lipoprotein levels, serum and tissue lipase activities, and lipid composition of tissues such as liver, nerve, kidney, and adrenal gland. Here we briefly describe the phenotypes and genetics of several mutants with blood and tissue lipid abnormalities, and then provide a more in-depth discussion of two mutations, fatty liver dystrophy (fld) and combined lipase deficiency (cld). Mice homozygous for the fld mutation exhibit fatty liver and hypertriglyceridemia during neonatal development, and a peripheral neuropathy that progresses throughout the lifetime of the animal. Combined lipase deficiency is characterized by a nearly complete absence of lipoprotein lipase and hepatic lipase activity resulting in neonatal lethality. Although the underlying genes for these two disorders have yet to be identified, candidates that have been implicated through the molecular and biochemical characterization of the mutants are discussed.