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The most prominent feature of the disease is a distinctive gait with stiffness of the hind limbs that can be seen as early as 3\u00a0weeks after birth. The disease is progressive. Histopathological examination had revealed dystrophic changes specifically in type I (slow) myofibres, while electron microscopy had demonstrated abundant nemaline bodies. Therefore, it was never certain whether the disease was a dystrophy or a congenital myopathy with dystrophic features. In this study, we performed whole genome sequencing of OCPMD sheep and identified a single base deletion at the splice donor site (+\u20091) of intron 13 in the type I myofibre-specific <jats:italic>TNNT1<\/jats:italic> gene (KT218690 c.614\u2009+\u20091delG). All affected sheep were homozygous for this variant. Examination of <jats:italic>TNNT1<\/jats:italic> splicing by RT-PCR showed intron retention and premature termination, which disrupts the highly conserved 14 amino acid C-terminus. The variant did not reduce TNNT1 protein levels or affect its localization but impaired its ability to modulate muscle contraction in response to Ca<jats:sup>2+<\/jats:sup> levels. Identification of the causative variant in <jats:italic>TNNT1<\/jats:italic> finally clarifies that the OCPMD sheep is in fact a large animal model of TNNT1 congenital myopathy. This model could now be used for testing molecular or gene therapies.<\/jats:p>","DOI":"10.1186\/s40478-020-01017-1","type":"journal-article","created":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T13:04:32Z","timestamp":1597928672000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Ovine congenital progressive muscular dystrophy (OCPMD) is a model of TNNT1 congenital myopathy"],"prefix":"10.1186","volume":"8","author":[{"given":"Joshua S.","family":"Clayton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elyshia L.","family":"McNamara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayley","family":"Goullee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Conijn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keren","family":"Muthsam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle C.","family":"Musk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Coote","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Kijas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison C.","family":"Testa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhonda L.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda J.","family":"O\u2019Hara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Groth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coen","family":"Ottenheijm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianina","family":"Ravenscroft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5111-3732","authenticated-orcid":false,"given":"Nigel G.","family":"Laing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen J.","family":"Nowak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,20]]},"reference":[{"key":"1017_CR1","first-page":"513","volume":"6","author":"MD McGavin","year":"1969","unstructured":"McGavin MD, Baynes ID (1969) A congenital progressive ovine muscular dystrophy. 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