Journal article
Loss of Bardet–Biedl syndrome proteins alters the morphology and function of motile cilia in airway epithelia
Proceedings of the National Academy of Sciences - PNAS, Vol.105(9), pp.3380-3385
03/04/2008
DOI: 10.1073/pnas.0712327105
PMCID: PMC2265193
PMID: 18299575
Abstract
Mutations in a group of genes that contribute to ciliary function cause Bardet–Biedl syndrome (BBS). Most studies of BBS have focused on primary, sensory cilia. Here, we asked whether loss of BBS proteins would also affect motile cilia lining the respiratory tract. We found that BBS genes were expressed in human airway epithelia, and BBS2 and BBS4 localized to cellular structures associated with motile cilia. Although BBS proteins were not required for ciliogenesis, their loss caused structural defects in a fraction of cilia covering mouse airway epithelia. The most common abnormality was bulges filled with vesicles near the tips of cilia. We discovered this same misshapen appearance in airway cilia from Bbs1, Bbs2, Bbs4, and Bbs6 mutant mice. The structural abnormalities were accompanied by functional defects; ciliary beat frequency was reduced in Bbs mutant mice. Previous reports suggested BBS might increase the incidence of asthma. However, compared with wild-type controls, neither airway hyperresponsiveness nor inflammation increased in Bbs2−/− or Bbs4−/− mice immunized with ovalbumin. Instead, these animals were partially protected from airway hyperresponsiveness. These results emphasize the role of BBS proteins in both the structure and function of motile cilia. They also invite additional scrutiny of motile cilia dysfunction in patients with this disease.
Details
- Title: Subtitle
- Loss of Bardet–Biedl syndrome proteins alters the morphology and function of motile cilia in airway epithelia
- Creators
- Alok S Shah - Departments of Internal MedicineSara L Farmen - Departments of Internal MedicineThomas O Moninger - Departments of Internal MedicineThomas R Businga - Departments of Internal MedicineMichael P Andrews - Pediatrics, andKevin Bugge - Pediatrics, andCharles C Searby - Pediatrics, andDarryl Nishimura - Pediatrics, andKim A Brogden - Department of Periodontics andJoel N Kline - Departments of Internal MedicineVal C Sheffield - Pediatrics, andMichael J Welsh - Departments of Internal Medicine
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.105(9), pp.3380-3385
- DOI
- 10.1073/pnas.0712327105
- PMID
- 18299575
- PMCID
- PMC2265193
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences
- Language
- English
- Date published
- 03/04/2008
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Occupational and Environmental Health; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Medical Genetics and Genomics; Neurosurgery; Periodontics; Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9984020792002771
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