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

Ichthyosis vulgaris is an autosomal dominant disorder of keratinizatio n characterized by mild hyperkeratosis and reduced or absent keratohya lin granules in the epidermis, Profilaggrin, a major component of kera tohyalin grannies, is reduced or absent from the skin of individuals w ith ichthyosis vulgaris. In this report, we have further characterized the molecular basis of low profilaggrin expression, which occurs in t his disease. fn situ hybridization revealed little profilaggrin mRNA i n ichthyosis vulgaris-affected epidermis, In keratinocytes cultured fr om the epidermis of affected individuals, the abundance of profilaggri n was reduced to less than 10% of normal controls, while the mRNA leve l 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 caus ed by aberrant transcription. Nucleotide sequencing of 5'-upstream, 3' -noncoding and flanking regions of the profilaggrin gene from ichthyos is vulgaris-affected individuals revealed only minor changes, probably due to genetic polymorphisms. Our results indicate that defective pro filaggrin expression in ichthyosis vulgaris is a result of selectively impaired posttranscriptional control.