Epidermolysis bullosa simplex: a paradigm for disorders of tissue fragility
Pierre A. Coulombe, … , Michelle L. Kerns, Elaine Fuchs
Pierre A. Coulombe, … , Michelle L. Kerns, Elaine Fuchs
Published July 1, 2009
Citation Information: J Clin Invest. 2009;119(7):1784-1793. https://doi.org/10.1172/JCI38177.
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Epidermolysis bullosa simplex: a paradigm for disorders of tissue fragility

Abstract

Epidermolysis bullosa (EB) simplex is a rare genetic condition typified by superficial bullous lesions that result from frictional trauma to the skin. Most cases are due to dominantly acting mutations in either keratin 14 (K14) or K5, the type I and II intermediate filament (IF) proteins tasked with forming a pancytoplasmic network of 10-nm filaments in basal keratinocytes of the epidermis and in other stratified epithelia. Defects in K5/K14 filament network architecture cause basal keratinocytes to become fragile and account for their trauma-induced rupture. Here we review how laboratory investigations centered on keratin biology have deepened our understanding of the etiology and pathophysiology of EB simplex and revealed novel avenues for its therapy.

Authors

Pierre A. Coulombe, Michelle L. Kerns, Elaine Fuchs

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Figure 2

Skin fragility in EB simplex and mouse models thereof.

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Skin fragility in EB simplex and mouse models thereof. (A) Example of tr...
(A) Example of trauma-induced bullous skin lesions (arrows) in the feet of a 2-month-old child diagnosed with EB simplex. Courtesy of Bernard Cohen (Johns Hopkins School of Medicine; photo copyright DermAtlas). (B) Massive skin blistering as seen in a K14-null mouse neonate. Front paws and facial area are severely affected (arrows). (C) A control littermate exhibits intact skin. (D and E) Micrographs from H&E-stained histological sections prepared from front paws of 2-day-old K14-null (D) and wild-type (E) mice. Fluid-filled blisters are obvious in the K14-null sample. Loss of epidermal integrity occurs near the basal layer of keratinocytes, the defining characteristic of EB simplex. The boxed region in E indicates 3 basal keratinocytes. hf, hair follicles. Scale bar: 100 μm.