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Published online 21 August 2000. doi:10.1083/jcb.150.4.921
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© The Rockefeller University Press, 0021-9525/2000//921 $5.00
The Journal of Cell Biology, Volume 150, Number 4, , 2000 921-928

Report

Introducing a Null Mutation in the Mouse K6{alpha} and K6β Genes Reveals Their Essential Structural Role in the Oral Mucosa



Pauline Wonga, Emma Colucci-Guyonb, Kenzo Takahashic, Changhong Gua, Charles Babinetb, and Pierre A. Coulombea

a Department of Biological Chemistry and Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
b Unité de Biologie du Développement, Institut Pasteur, 75724 Paris CEDEX 15, France
c Department of Dermatology, Kyoto University, Kyoto 606-8507, Japan
Department of Biological Chemistry, Johns Hopkins University School of Medicine, 725 N. Wolfe St., Baltimore, MD 21205.410 955 5759410 614 0510

coulombe{at}jhmi.edu

Mammalian genomes feature multiple genes encoding highly related keratin 6 (K6) isoforms. These type II keratins show a complex regulation with constitutive and inducible components in several stratified epithelia, including the oral mucosa and skin. Two functional genes, K6{alpha} and K6β, exist in a head-to-tail tandem array in mouse genomes. We inactivated these two genes simultaneously via targeting and homologous recombination. K6 null mice are viable and initially indistinguishable from their littermates. Starting at two to three days after birth, they show a growth delay associated with reduced milk intake and the presence of white plaques in the posterior region of dorsal tongue and upper palate. These regions are subjected to greater mechanical stress during suckling. Morphological analyses implicate the filiform papillae as being particularly sensitive to trauma in K6{alpha}/K6β null mice, and establish the complete absence of keratin filaments in their anterior compartment. All null mice die about a week after birth. These studies demonstrate an essential structural role for K6 isoforms in the oral mucosa, and implicate filiform papillae as being the major stress bearing structures in dorsal tongue epithelium.

Key Words: keratin • bullous diseases • skin • transgenic mouse • pachyonychia congenita

© 2000 The Rockefeller University Press

Abbreviations used in this paper: ES, embryonic stem cells; IF, intermediate filaments; K6, keratin 6; mK6{alpha}, mouse K6{alpha}; mK6β, mouse K6β; Neor, neomycin resistance; RT, reverse transcriptase; TK, thymidine kinase.


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