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 i s 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 i n neonatal mice without signs of fragility or wound-healing response. Howev er, there were profound changes in the composition of suprabasal keratin fi laments. K5/14 persisted suprabasally at elevated protein levels, whereas t heir mRNAs remained restricted to the basal keratinocytes. This indicated a novel mechanism regulating keratin turnover. Moreover, the amount of KI wa s 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 ele ctron microscopy. We suggest that these changes maintained epidermal integr ity. Furthermore, suprabasal keratinocytes contained larger keratohyalin gr anules similar to our previous K10T mice. A comparison of profilaggrin proc essing in K10T and K10(-/-) mice revealed an accumulation of filaggrin prec ursors in the former but not in the latter, suggesting a requirement of int act keratin filaments for the processing. The mild phenotype of K10(-/-) mi ce suggests that there is a considerable redundancy in the keratin gene fan -Lily.