A conditional smoothened (smo) allele on an inbred C57BL/6J genetic background has a hypomorphic smo mutant phenotype

We have introduced the floxed allele of Smoothened (Smo) carried by the mouse line Smo^tm2Amc into the C57BL/6J strain by serial backcross. Recapitulation of the Smo null phenotype was confirmed by deleting the allele using E2a-cre and intercrossing heterozygous Smo ± mice. No homozygous mutant embryos were identified at E9.5, suggesting the null phenotype is at least as severe as that observed on a mixed genetic background. While healthy and fertile homozygous floxed mice were regularly obtained after intercrosses, their numbers at weaning were reduced relative to Mendelian expectation, suggesting the unrecombined allele is itself hypomorphic. This hypothesis is supported by characterization of transcription of the floxed allele, which revealed that its expression was variably reduced relative to wild-type Smo.