CONCLUSION
We have made great progress in understanding the structure and function of the epidermis. Another challenge is to better elucidate the gene regulatory mechanisms and cell signaling pathways required for the development and maintenance of the skin. Identification of epigenetic factors and modifier genes will help to explain phenotypic variations and establish more precise genotype–phenotype correlations. This knowledge will form the foundation for the development of new therapeutic strategies for acquired and inherited skin diseases.
Additional table on Mouse models for human skin diseases due to abnormalities in structural and desmosomal proteins, available in our eBook (see inside front cover for access code).
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The generation of mouse models has significantly increased our under-standing of skin biology and the pathophysiology of genodermatoses. Animals harboring mutational “hot spots” that have been identified in humans are important for testing novel disease-targeted treatments and can help to bring new technologies closer to clinical use. For example, a reporter mouse model was developed to assess topical formulations that deliver short interfering RNAs (siRNAs) into the skin to silence dominant-negative mutant alleles.
Fig. 56.9 Filaggrin loss-of-function variants in ichthyosis vulgaris and atopic dermatitis. The filaggrin protein consists of several domains: an S100 Ca+-binding domain (yellow oval), a B-domain (beige octagon), two imperfect filaggrin repeats (green rectangles), 10 filaggrin repeats (blue numbered rectangles; some individuals have two copies of repeat 8 and/or 10), and a C-terminal domain (yellow hexagon). Mutations in filaggrin that have been identified in patients with ichthyosis vulgaris and atopic dermatitis are indicated.