A frameshift mutation within LAMC2 is responsible for Herlitz type junctional epidermolysis bullosa (HJEB) in black headed mutton sheep.

[junctional epidermolysis bullosa]

Junctional epidermolysis bullosa (JEB ) is a hereditary mechanobullous skin disease in humans and animals . A Herlitz type JEB was identified in German Black Headed Mutton (BHM ) sheep and affected lambs were reproduced in a breeding trial . Affected lambs showed skin and mucous membranes blistering and all affected lambs died within the first weeks of life . The pedigree data were consistent with a monogenic autosomal recessive inheritance . Immunofluorescence showed a reduced expression of laminin 5 protein which consists of 3 subunits encoded by the genes LAMA 3 , LAMB 3 and LAMC 2 . We screened these genes for polymorphisms . Linkage and genome-wide association analyses identified LAMC 2 as the most likely candidate for HJEB . A two base pair deletion within exon 18 of the LAMC 2 gene (FM 872310 :c .2746 delCA ) causes a frameshift mutation resulting in a premature stop codon (p .A 928 *) 13 triplets downstream of this mutation and in addition , introduces an alternative splicing of exon 18 LAMC 2 . This deletion showed a perfect co -segregation with HJEB in all 740 analysed BHM sheep . Identification of the LAMC 2 deletion means an animal model for HJEB is now available to develop therapeutic approaches of relevance to the human form of this disease .