Mutations in the gene encoding the low-density lipoprotein receptor LRP4 cause abnormal limb development in the mouse

Positional cloning of two recessive mutations of the mouse that cause polysyndactyly (dan and mdig—Chr 2) confirmed that the gene encoding MEGF7/LRP4, a member of the low-density lipoprotein receptor family, plays an essential role in the process of digit differentiation. Pathologies observed in the mutant mice provide insight into understanding the function(s) of LRP4 as a negative regulator of the Wnt–β-catenin signaling pathway and may help identify the genetic basis for common human disorders with similar phenotypes.