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PMID: 7523421 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Increased expression of keratin 16 causes anomalies in cytoarchitecture and keratinization in transgenic mouse skin.

The Journal of cell biology ·Vol. 127 ·No. 2 ·1994-10-00 ·Pages 505-20

Takahashi K, Folmer J, Coulombe PA

Abstract

Injury to epidermis and other stratified epithelia triggers profound but transient changes in the pattern of keratin expression. In postmitotic cells located at the wound edge, a strong induction of K6, K16, and K17 synthesis occurs at the expense of the keratins produced under the normal situation. The functional significance of these alterations in keratin expression is not known. Here, we report that overexpression of a wild-type human K16 gene in a tissue-specific fashion in transgenic mice causes aberrant keratinization of the hair follicle outer root sheath and proximal epidermis, and it leads to hyperproliferation and increased thickness of the living layers (acanthosis), as well as cornified layers (hyperkeratosis). The pathogenesis of lesions in transgenic mouse skin begins with a reorganization of keratin filaments in postmitotic keratinocytes, and it progresses in a transgene level-dependent fashion to include disruption of keratinocyte cytoarchitecture and structural alterations in desmosomes at the cell surface. No evidence of cell lysis could be found at the ultrastructural level. These results demonstrate that the disruption of the normal keratin profile caused by increased K16 expression interferes with the program of terminal differentiation in outer root sheath and epidermis. They further suggest that when present at sufficiently high intracellular levels, K16, along with K6 and K17, appear capable of inducing a reorganization of keratin filaments in the cytoplasm of skin epithelial cells.

Related Genes
K16
MeSH Terms
Acantholysis/pathology Amino Acid Sequence Animals Cell Adhesion Cytoskeleton/ultrastructure Desmosomes/ultrastructure Epidermis/metabolism,pathology Female Gene Expression Regulation Hair/metabolism Humans Keratinocytes/pathology Keratins/biosynthesis,genetics,metabolism Male Mice Mice, Transgenic Microscopy, Electron Molecular Sequence Data Phenotype Skin Diseases/etiology,pathology
Chemicals
Keratins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Takahashi K
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Folmer J
Coulombe P A
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.127.2.505
Published
1994-10-00
Pages
505-20
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2120213
Subset
IM
External Links
PubMed source DOI: 10.1083/jcb.127.2.505 PMC Full Text View journal details
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