Nature Genetics
36, 994 - 998 (2004)
Published online: 22 August 2004; | doi:10.1038/ng1418
Loss of BBS proteins causes anosmia in humans and defects in olfactory cilia structure and function in the mouseHeather M Kulaga1, Carmen C Leitch2, Erica R Eichers3, Jose L Badano2, Alysa Lesemann1, Bethan E Hoskins4, James R Lupski3, 5, 6, Philip L Beales4, Randall R Reed1
& Nicholas Katsanis2, 71
Howard Hughes Medical Institute and Department of Molecular Biology and Genetics, 533 Broadway Street Building, Johns Hopkins University, 733 N. Broadway, Baltimore, Maryland 21205, USA. 2
Institute of Genetic Medicine, 533 Broadway Street Building, Johns Hopkins University, 733 N. Broadway, Baltimore, Maryland 21205, USA. 3
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA. 4
Molecular Medicine Unit, Institute of Child Health, University College London, London WC1 1EH, UK. 5
Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA. 6
The Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030, USA. 7
Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland 21287, USA.
Correspondence should be addressed to Nicholas Katsanis katsanis@jhmi.eduDefects in cilia are associated with several human disorders, including Kartagener syndrome1, polycystic kidney disease2,
3, nephronophthisis4 and hydrocephalus5. We proposed that the pleiotropic phenotype of Bardet-Biedl syndrome (BBS), which encompasses retinal degeneration, truncal obesity, renal and limb malformations and developmental delay, is due to dysfunction of basal bodies and cilia6,
7. Here we show that individuals with BBS have partial or complete anosmia. To test whether this phenotype is caused by ciliary defects of olfactory sensory neurons, we examined mice with deletions of Bbs1 or Bbs4. Loss of function of either BBS protein affected the olfactory, but not the respiratory, epithelium, causing severe reduction of the ciliated border, disorganization of the dendritic microtubule network and trapping of olfactory ciliary proteins in dendrites and cell bodies. Our data indicate that BBS proteins have a role in the microtubule organization of mammalian ciliated cells and that anosmia might be a useful determinant of other pleiotropic disorders with a suspected ciliary involvement.
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