An intact keratin 5/keratin 14 intermediate filament cytoskeleton is vital for 
the integrity of basal keratinocytes and for the development and maintenance of 
epidermal structures. In patients with epidermolysis bullosa simplex 
Dowling-Meara (EBS-DM), heterozygous mutations in the keratin 14 gene in 
keratinocytes cause a cytoskeletal collapse leading to fragile cells susceptible 
to cellular stress. The primary aim of this work was to extend analysis of 
differentially expressed genes in an EBS-DM model cell line to obtain insights 
into the molecular consequences resulting from the keratin 14 mutation. In a 
first step, suppression subtractive hybridization (SSH), a powerful technology 
to enrich for differentially expressed genes, was used to identify genes whose 
up-regulation may be a direct or indirect result of the keratin 14 mutation, 
R125P. We discovered 55 candidate genes (SSH genes) that were further analysed 
by RTq-PCR. Of the 55 SSH genes, 14 (25.45%) were found to be congruently 
up-regulated. Bioinformatic analysis revealed significant enrichment of genes 
regulating epidermal development, migration, apoptosis and wound healing.