DECREASED PROFILAGGRIN EXPRESSION IN ICHTHYOSIS-VULGARIS IS A RESULT OF SELECTIVELY IMPAIRED POSTTRANSCRIPTIONAL CONTROL

Ichthyosis vulgaris is an autosomal dominant disorder of keratinization characterized by mild hyperkeratosis and reduced or absent keratohyalin granules in the epidermis, Profilaggrin, a major component of keratohyalin grannies, is reduced or absent from the skin of individuals with ichthyosis vulgaris. In this report, we have further characterized the molecular basis of low profilaggrin expression, which occurs in this disease. fn situ hybridization revealed little profilaggrin mRNA in ichthyosis vulgaris-affected epidermis, In keratinocytes cultured from the epidermis of affected individuals, the abundance of profilaggrin was reduced to less than 10% of normal controls, while the mRNA level was decreased to 30-60% of controls, Expression of K1 and loricrin, other markers of epidermal differentiation, were not affected, Nuclear run-on assays indicated that the decrease in mRNA levels was not caused by aberrant transcription. Nucleotide sequencing of 5'-upstream, 3'-noncoding and flanking regions of the profilaggrin gene from ichthyosis vulgaris-affected individuals revealed only minor changes, probably due to genetic polymorphisms. Our results indicate that defective profilaggrin expression in ichthyosis vulgaris is a result of selectively impaired posttranscriptional control.