scholarly journals Inversa Dystrophic Epidermolysis Bullosa Is Caused by Missense Mutations at Specific Positions of the Collagenic Domain of Collagen Type VII

2010 ◽  
Vol 130 (10) ◽  
pp. 2508-2511 ◽  
Author(s):  
Christine Chiaverini ◽  
Alexandra V. Charlesworth ◽  
Monia Youssef ◽  
Jean-François Cuny ◽  
Smail H. Rabia ◽  
...  
Keyword(s):  
Epidermolysis Bullosa ◽  
Collagen Type ◽  
Missense Mutations ◽  
Dystrophic Epidermolysis Bullosa ◽  
Collagen Type Vii

scholarly journals Mouse models for dominant dystrophic epidermolysis bullosa (DDEB) carrying common human point mutations recapitulate the human disease

2021 ◽  
Author(s):  
B. R. C. Smith ◽  
A. Nystrom ◽  
C. J. Nowell ◽  
I. Hausser ◽  
C. Gretzmeier ◽  
...  
Keyword(s):  
Mouse Models ◽  
Epidermolysis Bullosa ◽  
Severe Disease ◽  
Point Mutations ◽  
Missense Mutations ◽  
Dystrophic Epidermolysis Bullosa ◽  
Mild Phenotype ◽  
Growth And Survival ◽  
Skin Fragility ◽  
Collagen Vii

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 that closely resembles that seen in DDEB patients. Specifically, mice carrying these alleles show recurrent blistering that is first observed transiently around the mouth and paws in the early neonatal period and then again around the digits from 5-10 weeks of age. Histologically, the mice show micro-blistering and reduced collagen VII immunostaining. Biochemically, collagen VII from these mice displays reduced thermal stability, which we also observed to be the case for DDEB patients carrying the analogous mutations. Unlike previous rodent models of EB which frequently show early lethality and severe disease, these mouse models which to our knowledge are the first for DDEB show no reduction in growth and survival and – together with a relatively mild phenotype – represent a practically and ethically tractable tool for better understanding and treating EB.

scholarly journals Genetic Linkage Between the Collagen Type VII Gene COL7A1 and Pretibial Epidermolysis Bullosa with Lichenoid Features

1995 ◽  
Vol 104 (5) ◽  
pp. 803-805 ◽  
Author(s):  
Jean Marie Naeyaert ◽  
Lieve Nuytinck ◽  
Sylvia De Bie ◽  
Hilde Beele ◽  
André Kint ◽  
...  
Keyword(s):  
Epidermolysis Bullosa ◽  
Genetic Linkage ◽  
Collagen Type ◽  
Collagen Type Vii

scholarly journals Fluorescence overlay antigen mapping of the epidermal basement membrane zone: III. Topographic staining and effective resolution.

1995 ◽  
Vol 43 (7) ◽  
pp. 649-656 ◽  
Author(s):  
S Bruins ◽  
M C De Jong ◽  
K Heeres ◽  
M H Wilkinson ◽  
M F Jonkman ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Epidermolysis Bullosa ◽  
Collagen Type ◽  
Basement Membrane Zone ◽  
Resolving Power ◽  
Resolution Limit ◽  
Double Immunofluorescence ◽  
Collagen Type Vii ◽  
Epidermal Basement Membrane ◽  
Reference Markers

In this third study on the fluorescence overlay antigen mapping (FOAM) technique, we have addressed the question of which differences of antigen distributions close to the resolving power of the light microscope can be distinguished. An answer to this question should provide clues to future applications of the technique aiming at the topographic differentiation of IgG deposits displayed at the epidermal basement membrane zone (EBMZ) in certain bullous skin disorders. For the present purpose we have developed a topographic staining model in human skin, using structural EBMZ antigens as topographic reference markers. The distribution of these markers relative to one another is visualized in FOAM images obtained by selective double immunofluorescence tracing and videomicroscopic overlay imaging. The theoretical resolution limit of the technique is discussed and suggests an effective lower limit of some 60-65 nm. Although this limit is not reached under present conditions, our results show that it is possible to distinguish topographic differences of antigen distributions with an upper resolution limit of 200 +/- 50 nm. Furthermore, our findings indicate that collagen Type VII and beta 4 integrin are the most suitable molecules to serve as topographic reference markers in future applications of the technique aiming at the differentiation of bullous pemphigoid (BP) and epidermolysis bullosa acquisita (EBA). Preliminary results on this topic are most promising indeed.

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