a frameshift mutation within lamc2 is responsible for herlitz type junctional epidermolysis bullosa (hjeb) in black headed mutton sheep内移码突变lamc2负责herlitz交界表皮松解型大疱(hjeb)为首的黑羊羊.pdfVIP

A Frameshift Mutation within LAMC2 Is Responsible for Herlitz Type Junctional Epidermolysis Bullosa (HJEB) in Black Headed Mutton Sheep ¨ 1 1,2 ¨ 1 3 3 Stefanie Momke , Andrea Kerkmann , Anne Wohlke , Miriam Ostmeier , Marion Hewicker-Trautwein , 2 4 2 Martin Ganter , James Kijas , for the International Sheep Consortium, Ottmar Distl * 1 Institute for Animal Breeding and Genetics, University of Veterinary Medicine, Hannover, Germany, 2 Clinic for Swine and Small Ruminants, Forensic Medicine and Ambulatory Service, University of Veterinary Medicine, Hannover, Germany, 3 Institute for Pathology, University of Veterinary Medicine, Hannover, Germany, 4 Commonwealth Scientific and Industrial Research Organisation Livestock Industries, St. Lucia, Brisbane, Queensland, Australia Abstract 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 LAMA3, LAMB3 and LAMC2. We screened these genes for polymorphisms. Linkage and genome-wide association analyses identified LAMC2 as the most likely candidate for HJEB. A two base pair deletion within exon 18 of the