Tissue-specific expression and long-term deposition of human collagen VII in the skin of transgenic mice: implications for gene therapy

Abstract

We report the isolation of a cosmid clone containing the entire human COL7A1 gene in one piece. The ability of the genomic sequences within this clone to direct tissue-specific expression of human collagen VII in transgenic mice was tested. The data show that the gene construct is capable of directing expression of collagen VII in the skin of fetal and neonatal transgenic mice. Expression of COL7A1 in these mice was widespread, in a pattern consistent with that found in human tissues and was in parallel with that of the endogenous mouse gene. Immunostaining, using humanspecific antibodies, showed that human collagen VII protein

Recessive dystrophic epidermolysis bullosa results in painful small fibre neuropathy

“…Mutations in our cohort of patients are all located at the COL7A1 gene, which encodes the alpha-1 chain of type VII collagen a protein restricted to the basement zone beneath stratified squamous epithelia (Sat et al , 2000). Regarding expression of COL7A1 in the nervous system very little has been reported.…”

A non‐viral gene therapy for treatment of recessive dystrophic epidermolysis bullosa

“…S2). This indicated a therapeutically sufficient amount of protein could be produced in vivo as it has been reported for phenotypic correction a minimum 35%-50% of the standard amount of type VII collagen is required (6,7).…”

Gene Therapy for the COL7A1 Gene

“…Using a cosmid clone, carrying the entire COL7A1 gene, was also shown to be a promising way to direct expression of type VII collagen in skin in fetal and neonatal mice. The tested neonatal or fetal mice produced type VII collagen within the basal membrane zone of the skin showing a stable expression of the protein in vivo [52]. Microinjection of a P1-derived artificial chromosome (PAC) carrying the entire COL7A1 locus resulted in production of a procollagen VII similar to the authentic one by Mecklenbeck et al [53].…”