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Molecular and Cellular Biology, October 2001, p. 7047-7053, Vol. 21, No. 20
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.20.7047-7053.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Gene Targeting of Envoplakin, a Cytoskeletal Linker Protein and Precursor of the Epidermal Cornified Envelope

Arto Määttä,dagger Teresa DiColandrea,Dagger Karen Groot, and Fiona M. Watt*

Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom

Received 11 May 2001/Accepted 10 July 2001

Envoplakin, a member of the plakin family of cytoskeletal linker proteins, is localized in desmosomes of stratified epithelial cells and is a component of the epidermal cornified envelope. Gene targeting in mouse embryonic stem cells was used to generate a null allele of envoplakin. No envoplakin transcripts from the targeted allele could be detected in the skin of newborn mice. Mice homozygous for the targeted allele were born in the normal Mendelian ratio and were fertile. They did not develop any discernible pathological phenotype up to the age of 1 year. The ultrastructural appearance of cornified envelopes from adult epidermis was indistinguishable between wild-type and knockout mice, and there was no evidence that the absence of envoplakin affected the subcellular distribution of periplakin or desmoplakin, two other plakins found in desmosomes. The proportion of immature cornified envelopes in the epidermis of newborn mice was greater in envoplakin-null animals than in heterozygous littermates or wild-type mice, and the envelopes had a larger surface area. This correlated with a slight delay in barrier acquisition during embryonic development. We conclude that although envoplakin is part of the scaffolding on which the cornified envelope is assembled, it is not essential for envelope formation or epidermal barrier function.

* Corresponding author. Mailing address: Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom. Phone: 44 20 7269 3528. Fax: 44 20 7269 3078. E-mail: watt{at}icrf.icnet.uk.

dagger Present address: Department of Biological Sciences, University of Durham, Durham DH1 3LE, United Kingdom.

Dagger Present address: New Link Genetics, Ames, IA 50014.

Molecular and Cellular Biology, October 2001, p. 7047-7053, Vol. 21, No. 20
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.20.7047-7053.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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