Document Detail


Sperm-associated antigen-17 gene is essential for motile cilia function and neonatal survival.
MedLine Citation:
PMID:  23418344     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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-17 (Spag17) gene, which encodes a central pair (CP) protein present in the axonemes of cells with "9 + 2" 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.
Authors:
Maria Eugenia Teves; Zhibing Zhang; Richard M Costanzo; Scott C Henderson; Frank D Corwin; Jamal Zweit; Gobalakrishnan Sundaresan; Mark Subler; Fadi N Salloum; Bruce K Rubin; Jerome F Strauss
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  48     ISSN:  1535-4989     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-06-04     Completed Date:  2013-08-05     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  765-72     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Animals, Newborn
Axoneme / metabolism,  ultrastructure
Cell Movement*
Cilia / metabolism*,  ultrastructure
Female
Kartagener Syndrome / pathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Microscopy, Electron, Transmission
Microtubule Proteins / genetics,  metabolism*
Mutation
Nasal Mucosa / metabolism
Phenotype
Survival Analysis
Time Factors
Trachea / anatomy & histology,  metabolism,  pathology
Grant Support
ID/Acronym/Agency:
HD-37416/HD/NICHD NIH HHS; P30 CA016059/CA/NCI NIH HHS; P30 NS047463/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Microtubule Proteins; 0/SPAG6 protein, mouse
Comments/Corrections

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