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The\n                    <jats:italic>SP110<\/jats:italic>\n                    (speckled protein 110) gene has been demonstrated to be associated with host susceptibility to TB, but whether the susceptibility of dairy cattle to\n                    <jats:italic>M. bovis<\/jats:italic>\n                    is correlated with the bovine\n                    <jats:italic>SP110<\/jats:italic>\n                    (b\n                    <jats:italic>SP110<\/jats:italic>\n                    ) gene has not been investigated. Here, we demonstrated that the heightened susceptibility of dairy cattle to bTB was driven by species-specific alternative splicing of the bovine\n                    <jats:italic>SP110<\/jats:italic>\n                    (b\n                    <jats:italic>SP110<\/jats:italic>\n                    ) gene, which resulted in predominant expression of a truncated b\n                    <jats:italic>SP110c<\/jats:italic>\n                    variant lacking the SAND domain required for anti-bTB function. Compared to the other two splice variants of b\n                    <jats:italic>SP110<\/jats:italic>\n                    gene, b\n                    <jats:italic>SP110a<\/jats:italic>\n                    and b\n                    <jats:italic>SP110b<\/jats:italic>\n                    , b\n                    <jats:italic>SP110c<\/jats:italic>\n                    showing significantly reduced resistance to\n                    <jats:italic>M. bovis<\/jats:italic>\n                    . Mechanistically, the ruminant-specific absence of a upstream of the SAND exon (designated as the pre-SAND exon) affects alternative splicing of the b\n                    <jats:italic>SP110<\/jats:italic>\n                    gene, consequently promoting b\n                    <jats:italic>SP110c<\/jats:italic>\n                    production, while substituting this region with human\/equine sequences introduces suppress b\n                    <jats:italic>SP110c<\/jats:italic>\n                    and increase b\n                    <jats:italic>SP110a\/b<\/jats:italic>\n                    expression. Our study provides a new perspective on the genetic basis of the susceptibility of dairy cows to bTB and identifies a potential gene editing region for the breeding of tuberculosis-resistant dairy cows.\n                  <\/jats:p>","DOI":"10.1186\/s13567-025-01644-3","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T03:07:48Z","timestamp":1765508868000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Species-specific alternative splicing of SP110 drives tuberculosis susceptibility in cattle"],"prefix":"10.1186","volume":"57","author":[{"given":"Ajiao","family":"Fan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhunan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangchen","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zihan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanliang","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haoxin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanpeng","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"1644_CR1","doi-asserted-by":"publisher","first-page":"S5","DOI":"10.1016\/j.rvsc.2014.02.009","volume":"97","author":"S Rodriguez-Campos","year":"2014","unstructured":"Rodriguez-Campos S, Smith NH, Boniotti MB, Aranaz A (2014) Overview and phylogeny of Mycobacterium tuberculosis complex organisms: implications for diagnostics and legislation of bovine tuberculosis. 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