Exons 1 to 5 were replaced by a floxed neomycin cassette. Cre-mediated recombination removed the neo cassette. This strategy generated mice deficient in Dmkn beta and gamma isoforms, but still able to express the alpha isoform. Total absence of the beta and gamma isoforms was verified by RT-PCR analysis. Immunohistochemistry confirmed the absence of beta and gamma isoforms in the granular layer of neonatal epidermis in homozygous mutant mice. Quantitative RT-PCR revealed a significant increase in the expression of transcripts encoding the alpha isoform in the neonatal epidermis (8-fold) as well as in the ear skin (>3-fold) and tongue (>2-fold) of P15 homozygous mutant mice.