Mice that are homozygous for the Shhtm2Amc targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. This conditional mutant contains two loxP sites flanking exon 2 of the targeted allele. Cre-mediated recombination excises exon 2 and some surrounding intronic sequence, generating a null allele. When the conditional mutant is crossed with a ubiquitously-expressing Cre recombinase carrier to remove Shh activity in the early embryo, the resulting phenotype resembles the Shh null mutation. These conditional mutant mice may be mated to strains expressing Cre recombinase to study the effects of temporal and tissue-specific ablation of the targeted allele. This mutant mouse strain represents a model that may be useful in studies of developmental defects resulting from disruption of Shh-dependent pathways. When bred to a strain expressing Cre recombinase under the control of a tetracycline-responsive promoter element (see Stock No. 006224, 006234, 006244) and a strain expressing a tetracycline-controlled activator protein in the lung and respiratory epithelium (see Stock No. 006225), this mutant mouse strain provides an inducible model for use in studies of hedgehog signaling in respiratory system development. When bred to a strain with the targeted null allele (Stock No. 003318) and a strain expressing Cre recombinase in the skin and dental epithelium (Stock No. 004782), this mutant mouse strain may be useful in studies of hedgehog signaling and cell proliferation in the dental epithelium. When bred to a strain with the targeted null allele (Stock No. 003318) and a strain expressing Cre recombinase in the mesonephric duct and its developmental derivatives (Stock No. 004692), this mutant mouse strain may be useful in studies of hedgehog signalling and cell proliferation/differentiation in mesenchymal cells of the kidney. When bred to a strain expressing Cre recombinase in the nervous system (see Stock No. 003771 for example), this mutant mouse strain may be useful in studies of of hedgehog signaling in cortical interneurons.