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Molecular and Cellular Biology, July 2004, p. 6410-6418, Vol. 24, No. 14
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.14.6410-6418.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Periplakin Gene Targeting Reveals a Constituent of the Cornified Cell Envelope Dispensable for Normal Mouse Development

Sirpa Aho,1,{dagger}* Kehua Li,1,{dagger} Young Ryoo,1,{dagger} Clair McGee,1 Akemi Ishida-Yamamoto,2 Jouni Uitto,1 and John F. Klement1

Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania,1 Department of Dermatology, Asahikawa Medical College, Asahikawa 078-8510, Japan2

Received 5 February 2004/ Accepted 9 April 2004

The members of the plakin family of proteins serve as epidermal cytolinkers and components of cell-cell and cell-matrix adhesion complexes, i.e., desmosomes and hemidesmosomes, respectively. Periplakin is a recently characterized member of this family. Human and mouse periplakin genomic loci are conserved, and the proteins are highly homologous, suggesting a role for periplakin in vertebrate physiology. In order to evaluate the functional role of periplakin, we generated periplakin null mice through targeted homologous recombination of mouse embryonic stem cells, followed by development of Ppl–/– mice. Mice homozygous for the targeted allele were born in the expected Mendelian frequency, developed normally, possessed grossly normal epidermis and hair, and were healthy and fertile. The epidermal barrier appeared to develop normally during fetal days E15.5 to E16.5, and the cornified envelope and desmosomes in the newborn mice were ultrastructurally normal. No compensatory increase in the expression of other epithelial proteins was detected in the neonatal mouse epidermis lacking periplakin. Consequently, the primary role of periplakin may not relate to the physiology of the cornified cell envelope in epidermal keratinocytes but may reside in the challenges, which normal laboratory mice do not encounter.


* Corresponding author. Mailing address: Thomas Jefferson University, Department of Dermatology and Cutaneous Biology, BLSB 422, 233 South Tenth St., Philadelphia, PA 19107. Phone: (215) 503-2018. Fax: (215) 503-5788. E-mail: Sirpa.Aho{at}jefferson.edu.

{dagger} S.A., K.L., and Y.R. contributed equally to this work.


Molecular and Cellular Biology, July 2004, p. 6410-6418, Vol. 24, No. 14
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.14.6410-6418.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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