Journal Article

Creation and characterization of novel rat model for recessive dystrophic epidermolysis bullosa: Frameshift mutation of the Col7a1 gene leads to severe blistered phenotype

Eide, Cindy, McGrath, John, Lees, Christopher, Grzybowski, Michael, Stone, William, Strege, Chloe, Geurts, Aron M., Miller, William, Riddle, Megan, Tufa, Sara F., Seelig, Davis, Tolar, Jakub, Keene, Douglas R.

2024

Overview

Recessive dystrophic epidermolysis bullosa is a rare genodermatosis caused by a mutation of the Col7a1 gene. The Col7a1 gene codes for collagen type VII protein, a major component of anchoring fibrils. Mutations of the Col7a1 gene can cause aberrant collagen type VII formation, causing an associated lack or absence of anchoring fibrils. This presents clinically as chronic blistering, scarring, and fibrosis, often leading to the development of cutaneous squamous cell carcinoma. Patients also experience persistent pain and pruritus. Pain management and supportive bandaging remain the primary treatment options. The pathology of recessive dystrophic epidermolysis bullosa was first described in the 1980s, and there has since been a multitude of encouraging treatment options developed. However, in vivo research has been hindered by inadequate models of the disease. The various mouse models in existence possess longevity and surface area constraints, or do not adequately model a normal human disease state. In this paper, we describe a novel rat model of recessive dystrophic epidermolysis bullosa that offers an alternative to previous murine models. An 8-base pair deletion was induced in the Col7a1 gene of Lewis rats, which was subsequently found to cause a premature stop codon downstream. Homozygous mutants presented with a fragile and chronically blistered phenotype postnatally. Further histological analysis revealed subepidermal clefting and the absence of anchoring fibrils. The generation of this novel model offers researchers an easily maintained organism that possesses a larger surface area for experimental topical and transfused therapies to be tested, which may provide great utility in the future study of this debilitating disease.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Animal models / Animals / Biology and Life Sciences / Blister - genetics / Blister - pathology / Blistering / Collagen / Collagen (type VII) / Collagen Type VII - genetics / CRISPR / Disease Models, Animal / Dystrophic epidermolysis bullosa / Epidermolysis bullosa / Epidermolysis Bullosa Dystrophica - genetics / Epidermolysis Bullosa Dystrophica - pathology / Fibrils / Fibrosis / Frameshift Mutation / Gene deletion / Genes, Recessive / Genetic aspects / Genodermatosis / Genotype & phenotype / Health aspects / Inflammation / Male / Medical research / Medicine and Health Sciences / Medicine, Experimental / Mice / Microscopy / Mutation / Nonsense mutation / Pain / Phenotype / Phenotypes / Physiological aspects / Pruritus / Rats / Rats, Inbred Lew / Research and Analysis Methods / Risk factors / Skin - pathology / Squamous cell carcinoma / Stop codon / Surface area / Survival analysis / Temperature