Skip to main content
. Author manuscript; available in PMC: 2013 Mar 1.
Published in final edited form as: J Invest Dermatol. 2011 Dec 8;132(3 Pt 2):820–828. doi: 10.1038/jid.2011.389

Figure 3.

Figure 3

siRNA strategies for autosomal dominant keratin 6a disorders by targeting either mutant or both mutant/wild-type alleles. (a) In normal keratinocytes, synthesis of K6a (blue), K6b (red) and K6c (green) occurs; (b) in PC keratinocytes with a heterozygous missense mutation in KRT6A there is dominant-negative interference between the wild-type and mutant K6a protein that perturbs the keratin network and compromises cell integrity, leading to skin blistering as a result of minor trauma; (c) one siRNA approach is to target the mutant KRT6A allele to leave only residual wild-type KRT6A allele expression; (d) an alternative siRNA strategy is to silence all KRT6A, both mutant and wild-type – blistering does not occur in the absence of K6a because of functional redundancy with K6b and K6c, allowing normal intermediate filament network integrity.