Journal article

Mouse models for dominant dystrophic epidermolysis bullosa carrying common human point mutations recapitulate the human disease

Blake RC Smith, Alexander Nystroem, Cameron J Nowell, Ingrid Hausser, Christine Gretzmeier, Susan J Robertson, George A Varigos, Cristina Has, Johannes S Kern, Ken C Pang



Heterozygous missense mutations in the human COL7A1 gene - coding for collagen VII - lead to the rare, dominantly inherited skin disorder dominant dystrophic epidermolysis bullosa (DDEB) that is characterized by skin fragility, blistering, scarring and nail dystrophy. To better understand the pathophysiology of DDEB and develop more effective treatments, suitable mouse models for DDEB are required but to date none have existed. We identified the two most common COL7A1 mutations in DDEB patients (p.G2034R and p.G2043R) and used CRISPR to introduce the corresponding mutations into mouse Col7a1 (p.G2028R and p.G2037R). Dominant inheritance of either of these two alleles results in a phenotype t..

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Awarded by Australian Rotary Health

Funding Acknowledgements

This work was supported by a DEBRA Australia research grant as well as a Scientific Research Grant from the Australasian College of Dermatologists. K.C.P. was also supported by the Royal Children's Hospital Foundation; B.R.C.S. was supported by a Kerry Anderson/Rotary District 9650 PhD Scholarship from Australian Rotary Health. The generation of the Col7a1 mice used in this study was supported by the Australian Phenomics Network and the Australian Government through the National Collaborative Research Infrastructure Strategy program.