NATURALLY-OCCURRING MUTATIONS IN MICE AFFECTING LIPID TRANSPORT AND METABOLISM

Naturally occurring mutations in the mouse provide a unique resource f or identifying genes and characterizing proteins involved in lipid met abolism. Spontaneous mouse mutations have been described that affect v arious aspects of lipid metabolism, including cellular cholesterol hom eostasis, fatty acid metabolism, serum lipoprotein levels, serum and t issue lipase activities, and lipid composition of tissues such as live r, nerve, kidney, and adrenal gland. Here we briefly describe the phen otypes and genetics of several mutants with blood and tissue lipid abn ormalities, and then provide a more in-depth discussion of two mutatio ns, fatty liver dystrophy (fld) and combined lipase deficiency (cld). Mice homozygous for the fld mutation exhibit fatty liver and hypertrig lyceridemia during neonatal development, and a peripheral neuropathy t hat progresses throughout the lifetime of the animal. Combined lipase deficiency is characterized by a nearly complete absence of lipoprotei n lipase and hepatic lipase activity resulting in neonatal lethality. Although the underlying genes for these two disorders have yet to be i dentified, candidates that have been implicated through the molecular and biochemical characterization of the mutants are discussed.