huCOL7A1-c.6527dupC Mouse

Epidermolysis bullosa (EB) is a hereditary skin disease characterized by the formation of blisters and bullae on the skin and mucous membranes after minor trauma or friction. Common clinical symptoms include blisters, blood blisters, and erosion on the skin. According to the different sites of onset, hereditary EB can be divided into three types: Epidermolysis Bullosa Simplex (EBS), Junctional Epidermolysis Bullosa (JEB), and Dystrophic Epidermolysis Bullosa (DEB). Mutations in the COL7A1 gene are the cause of Dystrophic Epidermolysis Bullosa (DEB), and the different clinical phenotypes presented by DEB are related to the mutation sites and forms of the COL7A1 gene. The COL7A1 gene encodes type VII collagen, which forms anchoring fibrils that bind dermal tissue to epidermal tissue. Functional anchoring fibril deficiency caused by COL7A1 mutations makes the patient’s skin extremely fragile and easily blistered or torn due to minor friction or trauma. At present, at least 324 pathogenic mutations of the COL7A1 gene related to DEB have been found, including nonsense, missense, deletion, insertion, splicing, and regulation ^[1].

The current DEB treatment pipeline is mainly based on gene therapy and small nucleic acid drugs, including ASO drugs, siRNA drugs, and gene therapy based on CRISPR and AAV vector delivery. Among them, COL7A1 is the most important therapeutic target. B-Vec, developed by Krystal Biotech delivers functional COL7A1 genes to skin cells of DEB patients with COL7A1 mutations through HSV-1 vectors to produce functional proteins to promote wound healing, was the first approved gene therapy drug for the DEB. In addition, since most ASO, siRNA, and CRISPR-based therapies target human COL7A1 genes, considering the genetic differences between animals and humans, humanizing mouse genes will help promote further clinical translation of therapies targeting COL7A1. This strain is a disease model constructed by introducing a common recurrent mutation (c.6527dupC) of the COL7A1 gene in human diseases into the mouse Col7a1 humanized model (Catalog Number: C001428) ^[2]。The homozygous huCOL7A1-c.6527dupC mice exhibit a disease phenotype similar to human Dystrophic Epidermolysis Bullosa (DEB), and most mice die within 6 days after birth ^[3-7]. Leveraging its proprietary TurboKnockout fusion BAC recombination technology, Cyagen can also provide customized services for specific mutations to meet the experimental needs in pharmacology and other fields related to EB.