DEFICIENT OUTGROWTH OF THE URETERAL BUD UNDERLIES THE RENAL AGENESIS PHENOTYPE IN MICE MANIFESTING THE LIMB DEFORMITY (LD) MUTATION

Mice which are homozygous for the limb deformity (ld) mutation also ma nifest an incompletely penetrant unilateral or bilateral renal agenesi s phenotype. Intercross experiments suggest that the differences in pe netrance of the renal agenesis phenotype between homozygous mice with different ld alleles are due to intrinsic differences in the strength of the mutant alleles or to one or more closely linked modifying loci, and not to generalized differences in genetic background. Analysis of ld/ld embryos between embryonic days 11-13 reveals delayed outgrowth or complete absence of the ureteric bud, the inducer of metanephric me senchyme. Since explants of ld/ld metanephric mesenchyme differentiate in culture when apposed to embryonic spinal cord, we conclude that de ficient ureteric bud outgrowth is the morphologic basis for renal agen esis in ld/ld mice. However, since Id transcripts can be detected in b oth metanephric mesenchyme and ureteric bud, the molecular basis for t he deficiency in ureteric bud outgrowth could reside in either compone nt. (C) 1994 Wiley-Liss, Inc.