title: Periplakin gene targeting reveals a constituent of the cornified cell envelope dispensable for normal mouse development.
abstract: 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.
authors.affiliation: Department of Dermatology and Cutaneous Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA. Sirpa.Aho@jefferson.edu
authors.forename: Sirpa
authors.initials: S
authors.lastname: Aho
authors.forename: Kehua
authors.initials: K
authors.lastname: Li
authors.forename: Young
authors.initials: Y
authors.lastname: Ryoo
authors.forename: Clair
authors.initials: C
authors.lastname: McGee
authors.forename: Akemi
authors.initials: A
authors.lastname: Ishida-Yamamoto
authors.forename: Jouni
authors.initials: J
authors.lastname: Uitto
authors.forename: John F
authors.initials: JF
authors.lastname: Klement
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D051180:Desmoplakins; D003896:Desmosomes / Q000378:metabolism*; D004817:Epidermis / Q000254:growth & development* / Q000378:metabolism* / Q000648:ultrastructure; D018390:Gene Targeting; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice / Q000254:growth & development*; D018345:Mice, Knockout; D051179:Plakins; D051190:Plectin; D011498:Protein Precursors / Q000378:metabolism
chemical_list: D000199:Actins; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; C495332:PLEC protein, human; C491674:PPL protein, human; D051179:Plakins; C495333:Plec protein, mouse; D051190:Plectin; C110037:Ppl protein, mouse; D011498:Protein Precursors; C100754:envoplakin; C032253:involucrin