{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:00:12Z","timestamp":1787497212841,"version":"build-2736575974"},"reference-count":31,"publisher":"The Company of Biologists","issue":"2","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation","doi-asserted-by":"crossref","award":["82002238"],"award-info":[{"award-number":["82002238"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Central South University Third Xiangya Hospital"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Leucine Rich Repeat Containing protein 56 (LRRC56), also known as DNAAF12, is a member of the LRRC superfamily, whose dysfunction is associated with mucociliary clearance and laterality defects in humans. Here, we generated LRRC56-knockout mice using the CRISPR\/Cas9 nuclease system to specifically target exons 4-5 of the LRRC56 gene. We observed that homozygous LRRC56 gene deletion is definitely deleterious, as 27.8% of LRRC56\u2212\/\u2212 mice died before adulthood. Among the surviving LRRC56\u2212\/\u2212 mice, the most prominent phenotypes included hydrocephalus, situs inversus, male infertility, and bronchiectasis. Transmission electron microscopy revealed defects in dynein arms of cilia and disorganized axonemal structure in flagella. Immunofluorescence analysis similarly revealed the absence of inner and outer dynein arm markers DNALI1 and DNAI2 in the cilia. Heterozygous LRRC56+\/\u2212 mice developed normally, without exhibiting any symptoms of primary ciliary dyskinesia. In conclusion, the knockout of the LRRC56 gene in mice leads to a range of conditions consistent with primary ciliary dyskinesia. The absence of DNALI1 and DNAI2 signaling in knockout mouse cilia supports the critical role of the LRRC56 gene in dynein arm assembly.<\/jats:p>","DOI":"10.1242\/bio.061846","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T06:09:26Z","timestamp":1738822166000},"source":"Crossref","is-referenced-by-count":9,"title":["LRRC56 deletion causes primary ciliary dyskinesia in mice characterized by dynein arms defects"],"prefix":"10.1242","volume":"14","author":[{"given":"Ruolan","family":"Wu","sequence":"first","affiliation":[{"name":"The Third Xiangya Hospital of Central South University 1 Department of Laboratory Medicine , , Changsha 410005 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huilong","family":"Li","sequence":"additional","affiliation":[{"name":"The Third Xiangya Hospital of Central South University 1 Department of Laboratory Medicine , , Changsha 410005 ,","place":["China"]},{"name":"Guangxi Hospital Division of The First Affiliated Hospital, Sun Yat-sen University 2 Department of Laboratory Medicine , , Nanning 530021 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingyun","family":"Wu","sequence":"additional","affiliation":[{"name":"The Third Xiangya Hospital of Central South University 1 Department of Laboratory Medicine , , Changsha 410005 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Yang","sequence":"additional","affiliation":[{"name":"The Third Xiangya Hospital of Central South University 1 Department of Laboratory Medicine , , Changsha 410005 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueting","family":"Wan","sequence":"additional","affiliation":[{"name":"The Third Xiangya Hospital of Central South University 1 Department of Laboratory Medicine , , Changsha 410005 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9358-9146","authenticated-orcid":false,"given":"Yuan","family":"Wu","sequence":"additional","affiliation":[{"name":"The Third Xiangya Hospital of Central South University 1 Department of Laboratory Medicine , , Changsha 410005 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2025,2,5]]},"reference":[{"key":"2025020611080364100_BIO061846C1","doi-asserted-by":"publisher","first-page":"e28472","DOI":"10.7759\/cureus.28472","article-title":"Primary ciliary dyskinesia: phenotype resulting from a novel variant of LRRC56 gene","volume":"14","author":"Alasmari","year":"2022","journal-title":"Cureus"},{"key":"2025020611080364100_BIO061846C2","doi-asserted-by":"publisher","first-page":"e1009306","DOI":"10.1371\/journal.pgen.1009306","article-title":"Defects in the cytoplasmic assembly of axonemal dynein arms cause morphological abnormalities and dysmotility in sperm cells leading to male infertility","volume":"17","author":"Aprea","year":"2021","journal-title":"PLoS Genet."},{"key":"2025020611080364100_BIO061846C3","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/j.ajhg.2018.10.003","article-title":"Biallelic mutations in LRRC56, encoding a protein associated with intraflagellar transport, cause mucociliary clearance and laterality defects","volume":"103","author":"Bonnefoy","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"2025020611080364100_BIO061846C4","doi-asserted-by":"publisher","first-page":"D437","DOI":"10.1093\/nar\/gkaa1038","article-title":"RCSB protein data bank: powerful new tools for exploring 3D Structures of biological macromolecules for basic and applied research and education in fundamental biology, biomedicine, biotechnology, bioengineering and energy sciences","volume":"49","author":"Burley","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"2025020611080364100_BIO061846C5","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1038\/s41586-024-07476-z","article-title":"An alternative cell cycle coordinates multiciliated cell differentiation","volume":"630","author":"Choksi","year":"2024","journal-title":"Nature"},{"key":"2025020611080364100_BIO061846C6","doi-asserted-by":"publisher","first-page":"6595","DOI":"10.1038\/s41467-022-33820-w","article-title":"The inner junction protein CFAP20 functions in motile and non-motile cilia and is critical for vision","volume":"13","author":"Chrystal","year":"2022","journal-title":"Nat. Commun."},{"key":"2025020611080364100_BIO061846C7","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1002\/cm.21206","article-title":"Chlamydomonas axonemal dynein assembly locus ODA8 encodes a conserved flagellar protein needed for cytoplasmic maturation of outer dynein arm complexes","volume":"72","author":"Desai","year":"2015","journal-title":"Cytoskeleton (Hoboken)"},{"key":"2025020611080364100_BIO061846C8","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.ajhg.2011.06.003","article-title":"Disruption of a Ciliary B9 protein complex causes meckel syndrome","volume":"89","author":"Dowdle","year":"2011","journal-title":"Am. J. Hum. Genet."},{"key":"2025020611080364100_BIO061846C9","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1113\/JP281952","article-title":"The LRRC family of BK channel regulatory subunits: potential roles in health and disease","volume":"600","author":"Gonzalez-Perez","year":"2022","journal-title":"J. Physiol."},{"key":"2025020611080364100_BIO061846C10","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1016\/j.chest.2023.12.005","article-title":"Situs ambiguus is associated with adverse clinical outcomes in children with primary ciliary dyskinesia","volume":"165","author":"Kaspy","year":"2024","journal-title":"Chest"},{"key":"2025020611080364100_BIO061846C11","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1016\/j.devcel.2021.03.006","article-title":"RNA demethylation by FTO stabilizes the FOXJ1 mRNA for proper motile ciliogenesis","volume":"56","author":"Kim","year":"2021","journal-title":"Dev. Cell"},{"key":"2025020611080364100_BIO061846C12","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1186\/s12964-023-01135-y","article-title":"LRRC6 regulates biogenesis of motile cilia by aiding FOXJ1 translocation into the nucleus","volume":"21","author":"Kim","year":"2023","journal-title":"Cell Commun. Signal"},{"key":"2025020611080364100_BIO061846C13","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s40779-024-00560-5","article-title":"Congenital hydrocephalus: a review of recent advances in genetic etiology and molecular mechanisms","volume":"11","author":"Liu","year":"2024","journal-title":"Mil. Med. Res."},{"key":"2025020611080364100_BIO061846C14","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/j.ajhg.2009.10.018","article-title":"Deletions and point mutations of LRRC50 cause primary ciliary dyskinesia due to dynein arm defects","volume":"85","author":"Loges","year":"2009","journal-title":"Am. J. Hum. Genet."},{"key":"2025020611080364100_BIO061846C15","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/S2213-2600(19)30374-1","article-title":"Primary ciliary dyskinesia in the genomics age","volume":"8","author":"Lucas","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"2025020611080364100_BIO061846C16","doi-asserted-by":"publisher","first-page":"e166869","DOI":"10.1172\/jci.insight.166869","article-title":"Loss-of-function mutations in CFAP57 cause multiple morphological abnormalities of the flagella in humans and mice","volume":"8","author":"Ma","year":"2023","journal-title":"JCI Insight"},{"key":"2025020611080364100_BIO061846C17","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1038\/s41576-023-00587-9","article-title":"Primary cilia as dynamic and diverse signalling hubs in development and disease","volume":"24","author":"Mill","year":"2023","journal-title":"Nat. Rev. Genet."},{"key":"2025020611080364100_BIO061846C18","doi-asserted-by":"publisher","first-page":"31567","DOI":"10.1074\/jbc.M101760200","article-title":"Characterization of Sptrx, a novel member of the thioredoxin family specifically expressed in human spermatozoa","volume":"276","author":"Miranda-Vizuete","year":"2001","journal-title":"J. Biol. Chem."},{"key":"2025020611080364100_BIO061846C19","doi-asserted-by":"publisher","first-page":"4863","DOI":"10.1016\/j.cell.2022.12.005","article-title":"The gymnastics of intraflagellar transport complexes keeps trains running inside cilia","volume":"185","author":"Nachury","year":"2022","journal-title":"Cell"},{"key":"2025020611080364100_BIO061846C20","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1093\/humupd\/dmad003","article-title":"The impact of primary ciliary dyskinesia on female and male fertility: a narrative review","volume":"29","author":"Newman","year":"2023","journal-title":"Hum. Reprod. Update"},{"key":"2025020611080364100_BIO061846C21","doi-asserted-by":"publisher","first-page":"2301769","DOI":"10.1183\/13993003.01769-2023","article-title":"Analyses of 1236 genotyped primary ciliary dyskinesia individuals identify regional clusters of distinct DNA variants and significant genotype-phenotype correlations","volume":"64","author":"Raidt","year":"2024","journal-title":"Eur. Respir. J."},{"key":"2025020611080364100_BIO061846C22","doi-asserted-by":"publisher","first-page":"e3002468","DOI":"10.1371\/journal.pbio.3002468","article-title":"The forkhead transcription factor foxj1 controls vertebrate olfactory cilia biogenesis and sensory neuron differentiation","volume":"22","author":"Rayamajhi","year":"2024","journal-title":"PLoS Biol."},{"key":"2025020611080364100_BIO061846C23","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1046\/j.1365-2443.2001.00484.x","article-title":"Sptrx-2, a fusion protein composed of one thioredoxin and three tandemly repeated ndp-kinase domains is expressed in human testis germ cells","volume":"6","author":"Sadek","year":"2001","journal-title":"Genes Cells"},{"key":"2025020611080364100_BIO061846C24","doi-asserted-by":"publisher","first-page":"2002359","DOI":"10.1183\/13993003.02359-2020","article-title":"Topological data analysis reveals genotype-phenotype relationships in primary ciliary dyskinesia","volume":"58","author":"Shoemark","year":"2021","journal-title":"Eur. Respir. J."},{"key":"2025020611080364100_BIO061846C25","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1038\/s41572-020-0209-6","article-title":"Motile ciliopathies","volume":"6","author":"Wallmeier","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"2025020611080364100_BIO061846C26","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1038\/s41586-023-06140-2","article-title":"Axonemal structures reveal mechanoregulatory and disease mechanisms","volume":"618","author":"Walton","year":"2023","journal-title":"Nature"},{"key":"2025020611080364100_BIO061846C27","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1080\/15548627.2019.1615303","article-title":"LRRC59 modulates type I interferon signaling by restraining the SQSTM1\/P62-mediated autophagic degradation of pattern recognition receptor DDX58\/RIG-I","volume":"16","author":"Xian","year":"2020","journal-title":"Autophagy"},{"key":"2025020611080364100_BIO061846C28","doi-asserted-by":"publisher","first-page":"1716","DOI":"10.1016\/j.devcel.2023.08.025","article-title":"Chromatin remodeling of prostaglandin signaling in smooth muscle enables mouse embryo passage through the female reproductive tract","volume":"58","author":"Xin","year":"2023","journal-title":"Dev. Cell"},{"key":"2025020611080364100_BIO061846C29","doi-asserted-by":"publisher","first-page":"8525","DOI":"10.3390\/ijms23158525","article-title":"LRRC46 accumulates at the midpiece of sperm flagella and is essential for spermiogenesis and male fertility in mouse","volume":"23","author":"Yin","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"2025020611080364100_BIO061846C30","doi-asserted-by":"publisher","first-page":"e2102940118","DOI":"10.1073\/pnas.2102940118","article-title":"Oviductal motile cilia are essential for oocyte pickup but dispensable for sperm and embryo transport","volume":"118","author":"Yuan","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025020611080364100_BIO061846C31","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/nature13992","article-title":"A comparative encyclopedia of DNA elements in the mouse genome","volume":"515","author":"Yue","year":"2014","journal-title":"Nature"}],"container-title":["Biology Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/bio\/article-pdf\/doi\/10.1242\/bio.061846\/3617104\/bio061846.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/bio\/article-pdf\/doi\/10.1242\/bio.061846\/3617104\/bio061846.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T06:09:32Z","timestamp":1738822172000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/bio\/article\/14\/2\/bio061846\/365551\/LRRC56-deletion-causes-primary-ciliary-dyskinesia"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,5]]},"references-count":31,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2,15]]}},"URL":"https:\/\/doi.org\/10.1242\/bio.061846","relation":{},"ISSN":["2046-6390"],"issn-type":[{"value":"2046-6390","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,5]]},"article-number":"bio061846"}}