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 granules, 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. In 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.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				A. Sandilands, C. Sutherland, A. D. Irvine, and W. H. I. McLean Filaggrin in the frontline: role in skin barrier function and disease J. Cell Sci., May 1, 2009; 122(9): 1285 - 1294. [Abstract] [Full Text] [PDF]

				M. Takaishi, T. Makino, M. Morohashi, and N.-h. Huh Identification of Human Hornerin and Its Expression in Regenerating and Psoriatic Skin J. Biol. Chem., February 11, 2005; 280(6): 4696 - 4703. [Abstract] [Full Text] [PDF]

				J A Tlacuilo-Parra, E Guevara-Gutierrez, and M Salazar-Paramo Acquired ichthyosis associated with systemic lupus erythematosus Lupus, April 1, 2004; 13(4): 270 - 273. [Abstract] [PDF]

				T. Makino, M. Takaishi, M. Toyoda, M. Morohashi, and N.-h. Huh Expression of Hornerin in Stratified Squamous Epithelium in the Mouse: A Comparative Analysis with Profilaggrin J. Histochem. Cytochem., April 1, 2003; 51(4): 485 - 492. [Abstract] [Full Text] [PDF]

				T. Makino, M. Takaishi, M. Morohashi, and N.-h. Huh Hornerin, a Novel Profilaggrin-like Protein and Differentiation-specific Marker Isolated from Mouse Skin J. Biol. Chem., December 7, 2001; 276(50): 47445 - 47452. [Abstract] [Full Text] [PDF]

				I. Marenholz, M. Zirra, D. F. Fischer, C. Backendorf, A. Ziegler, and D. Mischke Identification of Human Epidermal Differentiation Complex (EDC)-Encoded Genes by Subtractive Hybridization of Entire YACs to a Gridded Keratinocyte cDNA Library Genome Res., March 1, 2001; 11(3): 341 - 355. [Abstract] [Full Text]

				R. B. Presland and B. A. Dale Epithelial Structural Proteins of the Skin and Oral Cavity: Function in Health and Disease Critical Reviews in Oral Biology & Medicine, January 1, 2000; 11(4): 383 - 408. [Abstract] [Full Text] [PDF]