LIMB AND KIDNEY DEFECTS IN LMX1B MUTANT MICE SUGGEST AN INVOLVEMENT OF LMX1B IN HUMAN NAIL-PATELLA SYNDROME

Dorsal-ventral limb patterning in vertebrates is thought to be control led by the LIM-homeodomain protein Lmx1b which is expressed in a spati ally and temporally restricted manner along the dorsal-ventral limb ax is(1,2). Here we describe the phenotype resulting from targeted disrup tion of Lmx1b. Our results demonstrate that Lmx1b is essential for the specification of dorsal limb fates at both the zeugopodal and autopod al level with prominent phenotypes including an absence of nails and p atellae. These features are similar to those present in a dominantly i nherited human condition called nail patella syndrome(3) (NPS), which also has renal involvement. Mouse Lmx1b maps to a region syntenic to t hat of the NPS gene(4), and kidneys of Lmx1b mutant mice exhibit patho logical changes similar to that observed in NPS (refs 5,6), Our result s demonstrate an essential function for Lmx1b in mouse limb and kidney development and suggest that NPS might result from mutations in the h uman LMX1B gene.