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-beta-catenin signaling pathway and may help identify the genetic basis for common human disorders with similar phenotypes.
Simon-Chazottes
Dominique
D
Unité de Génétique fonctionnelle de la Souris, Institut Pasteur, 75724 Paris Cedex 15, France.
Tutois
Sylvie
S
Kuehn
Michael
M
Evans
Martin
M
Bourgade
Franck
F
Cook
Sue
S
Davisson
Muriel T
MT
Guénet
Jean-Louis
JL
D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005260:Female; D005552:Forelimb / Q000002:abnormalities* / Q000000981:diagnostic imaging; D026502:LDL-Receptor Related Proteins; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009154:Mutation; D016366:Open Reading Frames; D011859:Radiography; D011973:Receptors, LDL / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D017422:Sequence Analysis, DNA; D013576:Syndactyly / Q000175:diagnosis / Q000235:genetics
D026502:LDL-Receptor Related Proteins; C116415:Lrp4 protein, mouse; D011973:Receptors, LDL