A severe congenital mechanobullous disease with dermolytic blistering and recessive inheritance is described in sheep. The affected animals of wild and inbred flocks of the breed Weisses Alpenschaf (WAS) have
blisters of skin, oral mucosa, tongue, and esophagus at birth or within the first week of life. Exungulation occurs early, and severe erosions in the mouth lead to difficulty in feeding. Electron microscopic examination revealed sub-lamina densa splitting in natural or fresh friction
blisters and absence of identifiable anchoring fibrils in clinically uninvolved skin.
Antigen mapping localized
laminin and
collagen IV to the
blister roof. Indirect immunofluorescence staining with
antibodies to
collagen VII, the major structural component of the anchoring fibrils, demonstrated a complete absence of reaction in clinically uninvolved tissues of the affected sheep, whereas in normal sheep a strong linear fluorescence was seen at the epithelial-mesenchymal basement membrane zone. Dermal extracts of normal sheep contained intact
collagen VII, but epidermal and dermal extracts from the affected sheep lacked this
collagen or its fragments in immunoblotting experiments. Based on genetic, clinical, ultrastructural, and immunochemical findings, the sheep disorder corresponds to the severe mutilating subtype of recessive
dystrophic epidermolysis bullosa in humans and can be used as an animal model to investigate the human disorder.