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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,
Teresa
DiColandrea,
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.

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

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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