A MUTATION IN THE LIPOPROTEIN-LIPASE GENE ASSOCIATED WITH HYPERLIPOPROTEINEMIA TYPE-T IN MINK - STUDIES ON LIPID AND LIPASE LEVELS IN HETEROZYGOTES

Severe hypertriglyceridemia was previously observed in mink. Affected animals had no detectable lipoprotein lipase activity, but normal amou nts of lipoprotein lipase protein in post-heparin plasma. We have now cloned cDNA for lipoprotein lipase from normal mink and identified a s ingle point mutation in the affected animals which most likely explain s the deficiency of active lipase. The mutation is located in exon 6 a nd results in a Pro214Leu substitution. In heterozygote mink the level s of lipoprotein lipase activity and mass in post-heparin plasma were lower than in normal mink, but could not be used to identify carriers of the mutation. In some tissues (heart, muscle, kidney and lung), lip oprotein lipase activity was decreased to about 50%. In adipose tissue there seemed to be a mechanism to compensate for the mutation, result ing in increased mass and approximately the same activity of lipoprote in lipase as in animals not carrying the mutation. Mink had high lipop rotein lipase activity and mass in kidneys, although the levels of mRN A in kidney were many fold lower than in adipose tissue. Mink had very low levels of cholesteryl eater transfer protein activity in plasma. This may contribute to the high levels of HDL in this animal species.