{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:48:30Z","timestamp":1790768910090,"version":"4.1.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2013,6,1]],"date-time":"2013-06-01T00:00:00Z","timestamp":1370044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Primary ciliary dyskinesia (PCD), resulting from defects in cilia assembly or motility, is caused by mutations in a number of genes encoding axonemal proteins. PCD phenotypes are variable, and include recurrent respiratory tract infections, bronchiectasis, hydrocephaly, situs inversus, and male infertility. We generated knockout mice for the sperm-associated antigen\u201317 (Spag17) gene, which encodes a central pair (CP) protein present in the axonemes of cells with \u201c9 + 2\u201d motile cilia or flagella. The targeting of Spag17 resulted in a severe phenotype characterized by immotile nasal and tracheal cilia, reduced clearance of nasal mucus, profound respiratory distress associated with lung fluid accumulation and disruption of the alveolar epithelium, cerebral ventricular expansion consistent with emerging hydrocephalus, failure to suckle, and neonatal demise within 12 hours of birth. Ultrastructural analysis revealed the loss of one CP microtubule in approximately one quarter of tracheal cilia axonemes, an absence of a C1 microtubule projection, and other less frequent CP structural abnormalities. SPAG6 and SPAG16 (CP proteins that interact with SPAG17) were increased in tracheal tissue from SPAG17-deficient mice. We conclude that Spag17 plays a critical role in the function and structure of motile cilia, and that neonatal lethality is likely explained by impaired airway mucociliary clearance.<\/jats:p>","DOI":"10.1165\/rcmb.2012-0362oc","type":"journal-article","created":{"date-parts":[[2013,2,15]],"date-time":"2013-02-15T22:23:49Z","timestamp":1360967029000},"page":"765-772","source":"Crossref","is-referenced-by-count":57,"title":["Sperm-Associated Antigen\u201317 Gene Is Essential for Motile Cilia Function and Neonatal Survival"],"prefix":"10.1093","volume":"48","author":[{"given":"Maria Eugenia","family":"Teves","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhibing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology"},{"name":"Department of Biochemistry and Molecular Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M.","family":"Costanzo","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott C.","family":"Henderson","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank D.","family":"Corwin","sequence":"additional","affiliation":[{"name":"Department of Radiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamal","family":"Zweit","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology"},{"name":"Department of Radiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gobalakrishnan","family":"Sundaresan","sequence":"additional","affiliation":[{"name":"Department of Radiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Subler","sequence":"additional","affiliation":[{"name":"Department of Human and Molecular Genetics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadi N.","family":"Salloum","sequence":"additional","affiliation":[{"name":"Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce K.","family":"Rubin","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics"},{"name":"Department of Pediatrics, Virginia Commonwealth University, Richmond, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Jerome F.","family":"Strauss","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology"},{"name":"Department of Biochemistry and Molecular Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,6,1]]},"reference":[{"key":"2026021904211564100_bib1","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/nrm3085","article-title":"Ciliogenesis: building the cell\u2019s antenna","volume":"12","author":"Ishikawa","year":"2011","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2026021904211564100_bib2","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.gene.2010.11.006","article-title":"Mechanisms of mammalian ciliary motility: insights from primary ciliary dyskinesia genetics","volume":"473","author":"Lee","year":"2011","journal-title":"Gene"},{"key":"2026021904211564100_bib3","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1083\/jcb.100.6.2008","article-title":"Substructure of inner dynein arms, radial spokes, and the central pair\/projection complex of cilia and flagella","volume":"100","author":"Goodenough","year":"1985","journal-title":"J Cell Biol"},{"key":"2026021904211564100_bib4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/(SICI)1097-0169(1997)38:1<1::AID-CM1>3.0.CO;2-C","article-title":"The role of central apparatus components in flagellar motility and microtubule assembly","volume":"38","author":"Smith","year":"1997","journal-title":"Cell Motil Cytoskeleton"},{"key":"2026021904211564100_bib5","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1083\/jcb.98.1.229","article-title":"Genetic dissection of the central pair microtubules of the flagella of Chlamydomonas reinhardtii","volume":"98","author":"Dutcher","year":"1984","journal-title":"J Cell Biol"},{"key":"2026021904211564100_bib6","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/S0168-9525(00)89123-4","article-title":"Flagellar assembly in two hundred and fifty easy-to-follow steps","volume":"11","author":"Dutcher","year":"1995","journal-title":"Trends Genet"},{"key":"2026021904211564100_bib7","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1093\/molehr\/gar034","article-title":"Sperm flagella: comparative and phylogenetic perspectives of protein components","volume":"17","author":"Inaba","year":"2011","journal-title":"Mol Hum Reprod"},{"key":"2026021904211564100_bib8","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1074\/mcp.M400177-MCP200","article-title":"Dissecting the axoneme interactome: the mammalian orthologue of Chlamydomonas PF6 interacts with sperm-associated antigen 6, the mammalian orthologue of Chlamydomonas PF16","volume":"4","author":"Zhang","year":"2005","journal-title":"Mol Cell Proteomics"},{"key":"2026021904211564100_bib9","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1091\/mbc.12.3.739","article-title":"The Chlamydomonas PF6 locus encodes a large alanine\/proline-rich polypeptide that is required for assembly of a central pair projection and regulates flagellar motility","volume":"12","author":"Rupp","year":"2001","journal-title":"Mol Biol Cell"},{"key":"2026021904211564100_bib10","doi-asserted-by":"crossref","first-page":"4655","DOI":"10.1242\/jcs.02585","article-title":"Calmodulin and PF6 are components of a complex that localizes to the C1 microtubule of the flagellar central apparatus","volume":"118","author":"Wargo","year":"2005","journal-title":"J Cell Sci"},{"key":"2026021904211564100_bib11","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1095\/biolreprod.107.063206","article-title":"A heterozygous mutation disrupting the Spag16 gene results in biochemical instability of central apparatus components of the human sperm axoneme","volume":"77","author":"Zhang","year":"2007","journal-title":"Biol Reprod"},{"key":"2026021904211564100_bib12","doi-asserted-by":"crossref","first-page":"6298","DOI":"10.1128\/MCB.22.17.6298-6305.2002","article-title":"Male infertility, impaired sperm motility, and hydrocephalus in mice deficient in sperm-associated antigen 6","volume":"22","author":"Sapiro","year":"2002","journal-title":"Mol Cell Biol"},{"key":"2026021904211564100_bib13","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1083\/jcb.200710162","article-title":"Mutations in Hydin impair ciliary motility in mice","volume":"180","author":"Lechtreck","year":"2008","journal-title":"J Cell Biol"},{"key":"2026021904211564100_bib14","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1128\/MCB.00354-07","article-title":"Primary ciliary dyskinesia in mice lacking the novel ciliary protein Pcdp1","volume":"28","author":"Lee","year":"2008","journal-title":"Mol Cell Biol"},{"key":"2026021904211564100_bib15","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1097\/GIM.0b013e3181a53562","article-title":"Clinical and genetic aspects of primary ciliary dyskinesia\/Kartagener syndrome","volume":"11","author":"Leigh","year":"2009","journal-title":"Genet Med"},{"key":"2026021904211564100_bib16","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1097\/GIM.0b013e318203cff2","article-title":"Next generation massively parallel sequencing of targeted exomes to identify genetic mutations in primary ciliary dyskinesia: implications for application to clinical testing","volume":"13","author":"Berg","year":"2011","journal-title":"Genet Med"},{"key":"2026021904211564100_bib17","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1095\/biolreprod.105.049254","article-title":"Deficiency of SPAG16L causes male infertility associated with impaired sperm motility","volume":"74","author":"Zhang","year":"2006","journal-title":"Biol Reprod"},{"key":"2026021904211564100_bib18","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0955-0674(02)00012-1","article-title":"The vertebrate primary cilium is a sensory organelle","volume":"15","author":"Pazour","year":"2003","journal-title":"Curr Opin Cell Biol"},{"key":"2026021904211564100_bib19","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.ajhg.2012.08.016","article-title":"Recessive Hydin mutations cause primary ciliary dyskinesia without randomization of left\u2013right body asymmetry","volume":"91","author":"Olbrich","year":"2012","journal-title":"Am J Hum Genet"},{"key":"2026021904211564100_bib20","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1165\/ajrcmb.23.1.4070","article-title":"Ciliogenesis and left\u2013right axis defects in Forkhead factor HFH-4\u2013null mice","volume":"23","author":"Brody","year":"2000","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2026021904211564100_bib21","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1093\/hmg\/11.6.715","article-title":"Loss of function of axonemal dynein Mdnah5 causes primary ciliary dyskinesia and hydrocephalus","volume":"11","author":"Ibanez-Tallon","year":"2002","journal-title":"Hum Mol Genet"},{"key":"2026021904211564100_bib22","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1002\/humu.22001","article-title":"Static respiratory cilia associated with mutations in Dnahc11\/Dnah11: a mouse model of PCD","volume":"33","author":"Lucas","year":"2012","journal-title":"Hum Mutat"},{"key":"2026021904211564100_bib23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2012\/856918","article-title":"Lung oxidative damage by hypoxia","volume":"2012","author":"Araneda","year":"2012","journal-title":"Oxid Med Cell Longev"},{"key":"2026021904211564100_bib24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/physrev.00040.2007","article-title":"Interpreting neonatal lethal phenotypes in mouse mutants: insights into gene function and human diseases","volume":"89","author":"Turgeon","year":"2009","journal-title":"Physiol Rev"},{"key":"2026021904211564100_bib25","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1002\/cm.21035","article-title":"Computer-assisted image analysis of human cilia and Chlamydomonas flagella reveals both similarities and differences in axoneme structure","volume":"69","author":"O\u2019Toole","year":"2012","journal-title":"Cytoskeleton (Hoboken)"},{"key":"2026021904211564100_bib26","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1002\/cm.21010","article-title":"Analyses of functional domains within the PF6 protein of the central apparatus reveal a role for PF6 sub-complex members in regulating flagellar beat frequency","volume":"69","author":"Goduti","year":"2012","journal-title":"Cytoskeleton (Hoboken)"},{"key":"2026021904211564100_bib27","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.ajhg.2009.01.011","article-title":"Mutations in radial spoke head protein genes RSPH9 and RSPH4A cause primary ciliary dyskinesia with central-microtubular\u2013pair abnormalities","volume":"84","author":"Castleman","year":"2009","journal-title":"Am J Hum Genet"},{"key":"2026021904211564100_bib28","doi-asserted-by":"crossref","first-page":"e33667","DOI":"10.1371\/journal.pone.0033667","article-title":"Mutations in radial spoke head genes and ultrastructural cilia defects in East-European cohort of primary ciliary dyskinesia patients","volume":"7","author":"Zietkiewicz","year":"2012","journal-title":"PLoS ONE"},{"key":"2026021904211564100_bib29","doi-asserted-by":"crossref","first-page":"12946","DOI":"10.1073\/pnas.0404280101","article-title":"Haploinsufficiency for the murine orthologue of Chlamydomonas PF20 disrupts spermatogenesis","volume":"101","author":"Zhang","year":"2004","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["American Journal of Respiratory Cell and Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/48\/6\/765\/66896879\/ajrcmb_48_6_765.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/48\/6\/765\/66896879\/ajrcmb_48_6_765.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T09:24:29Z","timestamp":1771493069000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article\/48\/6\/765\/8483423"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6,1]]},"references-count":29,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2013,6,1]]},"published-print":{"date-parts":[[2013,6,1]]}},"URL":"https:\/\/doi.org\/10.1165\/rcmb.2012-0362oc","relation":{},"ISSN":["1044-1549","1535-4989"],"issn-type":[{"value":"1044-1549","type":"print"},{"value":"1535-4989","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2013,6]]},"published":{"date-parts":[[2013,6,1]]}}}