A novel type hypertriglyceridemia observed in FLS mice.
The unique inborn hypertriglyceridemia seen in FLS (fatty liver Shionogi) mice was relieved by the administration of purified apolipoprotein (apo) C-II. Lipoprotein lipase (LPL) and its cofactor, apoC-II, play a pivotal role in VLDL metabolism. Therefore, we investigated the genetic background involved in this hypertriglyceridemia. Plasma levels of TG and total cholesterol as well as LPL activity were measured in male FLS mice and C57/BL6J mice. Agarose gel electrophoresis and fast protein liquid chromatography were used to analyze the lipoprotein profile. A cross experiment was done to determine the genetic background of hypertriglyceridemia observed in FLS mice. cDNA sequences of apoC-II and apoC-III of FLS mice were determined. Prealpha-lipoprotein was the predominant lipoprotein class in FLS mouse plasma. LPL activity remained in the range observed in C57/BL6J mice, and purified apoC-II transiently relieved FLS mice from hypertriglyceridemia. Prealpha-lipoproteinemia was inherited in an autosomal recessive manner. ApoC-III appeared to be a causal factor for this unique hypertriglyceridemia. Microsatellite analysis, however, revealed that the responsible chromosome was not 7; rather, apoC-III mapped onto chromosome 9. Therefore, we suggest apoC-III as a candidate causative factor for the hypertriglyceridemia observed in FLS mice because an excessive amount of apoC-III attenuates LPL activity in vivo and in vitro.
D000818:Animals; D053304:Apolipoprotein C-II; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000172:deficiency / Q000235:genetics / Q000627:therapeutic use; D001483:Base Sequence; D002784:Cholesterol / Q000097:blood; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000097:blood / Q000235:genetics; D005808:Genes, Recessive; D006801:Humans; D006953:Hyperlipoproteinemia Type IV / Q000097:blood* / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D014280:Triglycerides / Q000097:blood
D053304:Apolipoprotein C-II; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D018076:DNA, Complementary; D014280:Triglycerides; D002784:Cholesterol; D008071:Lipoprotein Lipase