Formation of a normal epidermis supported by increased stability of keratins 5 and 14 in keratin 10 null mice.
The expression of distinct keratin pairs during epidermal differentiation is assumed to fulfill specific and essential cytoskeletal functions. This is supported by a great variety of genodermatoses exhibiting tissue fragility because of keratin mutations. Here, we show that the loss of K10, the most prominent epidermal protein, allowed the formation of a normal epidermis in neonatal mice without signs of fragility or wound-healing response. However, there were profound changes in the composition of suprabasal keratin filaments. K5/14 persisted suprabasally at elevated protein levels, whereas their mRNAs remained restricted to the basal keratinocytes. This indicated a novel mechanism regulating keratin turnover. Moreover, the amount of K1 was reduced. In the absence of its natural partner we observed the formation of a minor amount of novel K1/14/15 filaments as revealed by immunogold electron microscopy. We suggest that these changes maintained epidermal integrity. Furthermore, suprabasal keratinocytes contained larger keratohyalin granules similar to our previous K10T mice. A comparison of profilaggrin processing in K10T and K10(-/-) mice revealed an accumulation of filaggrin precursors in the former but not in the latter, suggesting a requirement of intact keratin filaments for the processing. The mild phenotype of K10(-/-) mice suggests that there is a considerable redundancy in the keratin gene family.
Reichelt
J
J
Institute of Genetics, University of Bonn, 53117 Bonn, Germany.
Büssow
H
H
Grund
C
C
Magin
T M
TM
D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern; D015153:Blotting, Western; D015180:Electrophoresis, Gel, Two-Dimensional; D004817:Epidermis / Q000378:metabolism* / Q000648:ultrastructure; D000091344:Filaggrin Proteins; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007381:Intermediate Filament Proteins / Q000737:chemistry; D053550:Keratin-10; D053547:Keratin-14; D053569:Keratin-15; D053555:Keratin-5; D007633:Keratins / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D005810:Multigene Family; D011498:Protein Precursors / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D014945:Wound Healing
D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D053547:Keratin-14; D053569:Keratin-15; D053555:Keratin-5; C507491:Krt10 protein, mouse; C507446:Krt14 protein, mouse; C492053:Krt15 protein, mouse; D011498:Protein Precursors; D012333:RNA, Messenger; D053550:Keratin-10; D007633:Keratins