Mice Expressing Only Covalent Dimeric Heparin Binding-deficient Lipoprotein Lipase

Lipoprotein lipase (LpL) hydrolyzes triglycerides of circulating lipoproteins while bound as homodimers to endothelial cell surface heparan sulfate proteoglycans. This primarily occurs in the capillary beds of muscle and adipose tissue. By creating a mouse line that expresses covalent dimers of heparin-binding deficient LpL (hLpLHBM-Dimer) in muscle, we confirmed in vivo that linking two LpL monomers in a head to tail configuration creates a functional LpL. The hLpLHBM-Dimer transgene produced abundant activity and protein in muscle, and the LpL was the expected size of a dimer (approximately 110 kDa). Unlike the heparin-binding mutant monomer, hLpLHBM-Dimer had the same stability as nonmut…