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Alok Shah

Mentor: Michael Welsh, M.D.
Lab Phone: 335-6540

The role of Bardet-Biedl Syndrome (BBS) protein in moltile cilia morphology and function

Bardet-Biedl Syndrome (BBS) is a rare autosomal recessive disorder with diverse phenotypes including obesity, retinopathy, polydactyly, and renal abnormalities. Asthma is also reported in BBS patients. We found that several BBS genes are expressed in human airway epithelia. To test the hypothesis that loss of BBS might predispose to asthma, we tested BBS2 and BBS4 null mice in an ovalbumin-induced airway hyperresponsiveness model. Our data show that disruption of these BBS genes did not increase airway hyperresponsiveness. Moreover, there were minimal differences between wild-type and BBS null mice in bronchoalveolar lavage cell counts and inflammatory cytokine levels. Previous studies suggest that BBS genes are involved in the function of primary (non-motile) cilia. Although motile cilia show many of the same components as primary cilia, whether loss of BBS proteins alters motile cilia and lung function remains unknown. Using scanning electron microscopy, we found that airway epithelia from BBS null mice contained cilia, but the loss of Bbs1, -2, -4 or -6 produced abnormal structure in a small proportion of motile cilia. We observed defects both in vitro and in vivo, and the abnormalities were heterogeneous both for cilia on an individual cell and between cells. Using transmission electron microscopy, we found that airway cilia from Bbs4 null mice contained bulges with a buildup of electron-dense particles. Airway epithelia from Bbs4 null and Bbs1 mutant mice also showed slower ciliary beat frequency than wild-type cilia. These data show that BBS proteins play an important role in maintaining normal structure and function of motile cilia in airway epithelia.


Shah, A.S., Farmen, S.L., Moninger, T.O., Andrews, M.P., Businga, T.R., Searby, C.C., Nishimura, D., Brogden, K.A., Kline, J. N., Sheffield, V.C., and Welsh, M.J. Loss of Bardet-Biedl protein alters the morphology and function of motile cilia in airway epithelia. American Society for Cell Biology Annual Meeting, 2007.


Shah AS, Farmen SL, Moninger TO, Businga TR, Andrews MP, Bugge K, Searby CC, Nishimura D, Brogden KA, Kline JN, Sheffield VC, Welsh MJ. Loss of Bardet-Biedl syndrome proteins alters the morphology and function of motile cilia in airway epithelia. Proc Natl Acad Sci U S A., 2008, 105(9):3380-5. Epub 2008, PMCID: PMC2265193, PMID: 18299575

Shah AS, Ben-Shahar Y, Moninger TO, Kline JN, Welsh MJ. Motile Cilia of Human Airway Epithelia Are Chemosensory. Science., 2009, 28;325(5944):1131-4. PMID: 19628819.

Honors and Awards

  • Predoctoral Travel Award from the American Society for Cell Biology, 2007. Best Poster Award receiv