OUT OF BALANCE - CONSEQUENCES OF A PARTIAL KERATIN-10 KNOCKOUT

Citation
J. Reichelt et al., OUT OF BALANCE - CONSEQUENCES OF A PARTIAL KERATIN-10 KNOCKOUT, Journal of Cell Science, 110, 1997, pp. 2175-2186
Citations number
67
Categorie Soggetti
Cell Biology
Journal title
ISSN journal
00219533
Volume
110
Year of publication
1997
Part
18
Pages
2175 - 2186
Database
ISI
SICI code
0021-9533(1997)110:<2175:OOB-CO>2.0.ZU;2-A
Abstract
Recently we generated keratin 10 knockout mice which provided a valuab le model for the dominantly inherited skin disorder epidermolytic hype rkeratosis, Here we investigated the molecular basis for their phenoty pe, Hetero- and homozygotes expressed a truncated keratin 10 peptide w hich has been identified directly by microsequencing. Epitope mapping of monoclonal antibodies to keratin 10T enabled us to study its distri bution relative to keratin 6, which is highly expressed in keratin 10 knockout mice, by double-immunogold electron microscopy. This revealed that keratin 10T was restricted to complexes with keratin 1 but did n ot mix with keratin 6. The latter did not form extended filaments with keratins 16/17 but aggregates, Keratins 6/16 were unable to compensat e for the lack of normal keratin 1/10 filaments, Remarkably keratin 6 aggregates strictly colocalized with keratohyalin granules. Residual k eratin 1/10T clumps were located in the cell periphery and at desmosom es which maintained a normal architecture, Surprisingly keratin 2e, a keratin tailored to sustain mechanical stress, was completely lost in paw sole epidermis of homozygous keratin 10 knockout mice, pointing to keratin 10 as its partner. The selective pairing of keratin 10T and t he loss of keratin 2e indicate that in vivo keratins are less promiscu ous than in vitro. Skin fragility in keratin 10 knockout mice and in e pidermolytic hyperkeratosis is probably the consequence of two complem enting mechanisms namely a decrease of normal keratin 1/10 filaments a nd an increase in keratins 6/16 with a poor filament-forming capacity.