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 controlled by the LIM-homeodomain protein Lmx1b which is expressed in a spatially and temporally restricted manner along the dorsal-ventral limb axis. Here we describe the phenotype resulting from targeted disruption of Lmx1b. Our results demonstrate that Lmx1b is essential for the specification of dorsal limb fates at both the zeugopodal and autopodal level with prominent phenotypes including an absence of nails and patellae. These features are similar to those present in a dominantly inherited human condition called nail patella syndrome (NPS), which also has renal involvement. Mouse Lmx1b maps to a region syntenic to that of the NPS gene, and kidneys of Lmx1b mutant mice exhibit pathological changes similar to that observed in NPS (refs 5,6). Our results demonstrate an essential function for Lmx1b in mouse limb and kidney development and suggest that NPS might result from mutations in the human LMX1B gene.