title: A mutation in bovine keratin 5 causing epidermolysis bullosa simplex, transmitted by a mosaic sire.
abstract: A mechanobullous skin disorder was identified in the progeny of a 3-y-old Friesian-Jersey crossbred bull. The condition presented as loss of skin and mucosa from contact areas and inflammation. Examination of skin samples under light microscopy revealed separation of the epidermis from the dermis. Electron microscopic analysis refined the site of cleavage to above the basement membrane involving lysis of basal keratinocytes. These observations were consistent with the simplex form of epidermolysis bullosa (EB) in humans. Candidate genes based on human gene mutations were assessed, resulting in keratin 5 being identified as the most likely candidate gene. The sequence of bovine keratin 5 was established and sequencing led to identification of a G to A substitution in all affected animals. This mutation leads to an amino acid change of glutamic acid to lysine in the final E (478) of the KLLEGE motif of the protein. The sire carried a de novo mutation and was mosaic, explaining his asymptomatic status and the less than expected frequency of affected offspring. Remarkably, the same mutation has been previously described in EB simplex in humans.
authors.affiliation: ViaLactia Biosciences (NZ) Ltd, Auckland, New Zealand.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Ford
authors.forename: Angela M
authors.initials: AM
authors.lastname: Stanfield
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Spelman
authors.forename: Bronwyn
authors.initials: B
authors.lastname: Smits
authors.forename: Alexandra E L
authors.initials: AE
authors.lastname: Ankersmidt-Udy
authors.forename: Kenneth
authors.initials: K
authors.lastname: Cottier
authors.forename: Hilary
authors.initials: H
authors.lastname: Holloway
authors.forename: Adrian
authors.initials: A
authors.lastname: Walden
authors.forename: Muhannad
authors.initials: M
authors.lastname: Al-Wahb
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Bohm
authors.forename: Russell G
authors.initials: RG
authors.lastname: Snell
authors.forename: Greg T
authors.initials: GT
authors.lastname: Sutherland
mesh_terms: D020816:Amino Acid Motifs; D019943:Amino Acid Substitution; D000818:Animals; D000831:Animals, Newborn; D002417:Cattle; D002418:Cattle Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002874:Chromosome Mapping; D016110:Epidermolysis Bullosa Simplex / Q000662:veterinary*; D005260:Female; D018698:Glutamic Acid; D053555:Keratin-5; D007633:Keratins / Q000235:genetics*; D008239:Lysine; D008297:Male; D008854:Microscopy, Electron; D009030:Mosaicism; D009154:Mutation; D010375:Pedigree
chemical_list: C503940:KRT5 protein, human; D053555:Keratin-5; D018698:Glutamic Acid; D007633:Keratins; D008239:Lysine