Introducing a null mutation in the mouse K6 alpha and K6 beta genes reveals their essential structural role in the oral mucosa

Mammalian genomes feature multiple genes encoding highly related keratin 6 (K6) isoforms,These type II keratins show a complex regulation with constit utive and inducible components in several stratified epithelia, including t he oral mucosa and skin. Two functional genes, K6 alpha and K6 beta, exist in a head-to-tail tandem array in mouse genomes. We inactivated these two g enes simultaneously via targeting and homologous recombination. K6 null mic e are viable and initially indistinguishable from their littermates. Starti ng at two to three days after birth, they show a growth delay associated wi th reduced milk intake and the presence of white plaques in the posterior r egion of dorsal tongue and upper palate. These regions are subjected to gre ater mechanical stress during suckling. Morphological analyses implicate th e filiform papillae as being particularly sensitive to trauma in K6 alpha/K 6 beta null mice, and establish the complete absence of keratin filaments i n their anterior compartment. All null mice die about a week after birth, T hese studies demonstrate an essential structural role for K6 isoforms in th e oral mucosa, and implicate filiform papillae as being the major stress be aring structures in dorsal tongue epithelium.