{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T14:10:21Z","timestamp":1787580621399,"version":"build-2736575974"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"University of Bern"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Appl Genetics"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Epidermolysis bullosa (EB) is a group of inherited skin disorders characterized by skin fragility and blistering. Here, four Bleu du Maine lambs, sired by one ram, were diagnosed with EB very early in life. Due to the severity of the clinical signs, the lambs had to be euthanized. The affected lambs exhibited hoof sloughing and multiple ulcerations on the head, oral cavity, skin over the joints, and the ruminal pillars. Histopathology showed abrupt subepidermal clefts, epidermal detachment directly above the basal membrane, and ulcerations consistent with junctional EB (JEB). Two cases underwent whole-genome sequencing (WGS) to identify the genetic cause. Genomic analyses with the hypothesis of autosomal recessive inheritance identified the most likely pathogenic homozygous 1-bp deletion in the <jats:italic>LAMB3<\/jats:italic> gene (NC_056065.1:g.73166198delG). Recessive forms of JEB in humans and dogs are caused by variants in <jats:italic>LAMB3<\/jats:italic> gene, which encodes \u03b23 subunit of laminin 332, a critical component of the epidermal basal membrane. The ovine frameshift variant putatively introduces a premature stop codon and disrupts the donor splice site of exon 20. The variant allele was homozygous in both sequenced cases and heterozygous in three unaffected close relatives and was absent in 1075 unrelated control sheep of various other breeds. This study highlights the importance of genetic investigation in veterinary diagnostics of and represents the first report of a <jats:italic>LAMB3<\/jats:italic>-related recessive EB in sheep. The findings enable genetic testing to inform breeding strategies and provide a second spontaneous large animal model for <jats:italic>LAMB3<\/jats:italic>-related JEB in humans.<\/jats:p>","DOI":"10.1007\/s13353-025-00957-5","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T05:09:20Z","timestamp":1742274560000},"page":"709-714","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A homozygous LAMB3 frameshift variant in junctional epidermolysis bullosa-affected Bleu du Maine sheep"],"prefix":"10.1007","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6521-1285","authenticated-orcid":false,"given":"Anna","family":"Letko","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7445-6508","authenticated-orcid":false,"given":"Liesbeth","family":"Harkema","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9517-6866","authenticated-orcid":false,"given":"Karianne","family":"Peterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1957-3664","authenticated-orcid":false,"given":"Reinie","family":"Dijkman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9773-522X","authenticated-orcid":false,"given":"Cord","family":"Dr\u00f6gem\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"957_CR1","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1111\/J.1365-3164.2005.00420.X","volume":"16","author":"Z Alhaidari","year":"2005","unstructured":"Alhaidari Z, Olivry T, Spadafora A et al (2005) Junctional epidermolysis bullosa in two domestic shorthair kittens. 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All live animals were blood sampled for diagnostic purposes on the farms to determine the cause of the disease. All other samples were obtained at postmortem examination of affected animals after euthanasia on humane grounds and were submitted by the owner for laboratory diagnostic investigation.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}