@article{80dbb604908b421bbc831d8a70032f75,
title = "The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formation",
abstract = "Primary ciliary dyskinesia (PCD) is a genetically heterogeneous autosomal recessive disorder characterized by recurrent infections of the respiratory tract associated with the abnormal function of motile cilia. Approximately half of individuals with PCD also have alterations in the left-right organization of their internal organ positioning, including situs inversus and situs ambiguous (Kartagener's syndrome). Here, we identify an uncharacterized coiled-coil domain containing a protein, CCDC40, essential for correct left-right patterning in mouse, zebrafish and human. In mouse and zebrafish, Ccdc40 is expressed in tissues that contain motile cilia, and mutations in Ccdc40 result in cilia with reduced ranges of motility. We further show that CCDC40 mutations in humans result in a variant of PCD characterized by misplacement of the central pair of microtubules and defective assembly of inner dynein arms and dynein regulatory complexes. CCDC40 localizes to motile cilia and the apical cytoplasm and is required for axonemal recruitment of CCDC39, disruption of which underlies a similar variant of PCD.",
author = "Anita Becker-Heck and Zohn, {Irene E.} and Noriko Okabe and Andrew Pollock and Lenhart, {Kari Baker} and Jessica Sullivan-Brown and Jason McSheene and Loges, {Niki T.} and Heike Olbrich and Karsten Haeffner and Manfred Fliegauf and Judith Horvath and Richard Reinhardt and Nielsen, {Kim G.} and Marthin, {June K.} and Gyorgy Baktai and Anderson, {Kathryn V.} and Robert Geisler and Lee Niswander and Heymut Omran and Burdine, {Rebecca D.}",
note = "Funding Information: We thank the German subject support group {\textquoteleft}Kartagener Syndrom und Primaere Ciliaere Dyskinesie e.V.{\textquoteright}, S. Glaser for the initial genomic mapping of lok, J. Liu for help with imaging Ccdc40 protein expression in the mouse node, L. Bulwith, A. Heer, C. Kopp, D. Nergenau and K. Sutter for excellent technical assistance, and D. Bosco for zebrafish facility maintenance. We also thank M. Griese (Munich), E.v. Mutius (Munich), T. Nuesslein (Koblenz), N. Schwerk (Hannover), S. Reithmayr (Vienna), H. Seithe (Nuernberg) and M. Stern (Tuebingen) for supporting the study. The lnks mutant mouse line was established as part of the SloanKettering Institute Mouse Project (R37HD035455). This work was supported by the Basil O{\textquoteright}Connor Award from the March of Dimes, the Young Investigator Award from the Spina Bifida Association and R01HD058629 to I.E.Z.; the German Human Genome Project DHGP grant 01 KW9919 to R.G.; the Howard Hughes Medical Institute to L.N.; {\textquoteleft}Deutsche Forschungsgemeinschaft{\textquoteright} DFG Om 6/4, GRK1104 and the SFB592 to H.O.; and NICHDR01HD048584 to R.D.B.",
year = "2011",
month = jan,
doi = "10.1038/ng.727",
language = "English (US)",
volume = "43",
pages = "79--84",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Research",
number = "1",
}