The genetics of fluttering cilia
It is here that the dog steps in. Individuals within the same breed being very closely related, the breed can be considered as a single large family. ‘Studying PCD in a breed of dog comes down to studying a genetically homogenous disease. The genetics of diseases within it is comfortably more simplified in comparison with humans,’ explains the professor. From prenatal diagnosis to gene therapy
Once the mutations of CCDC39 had been detected what remained was an understanding of how they affect the movement of vibrant cilia. ‘We could observe that the loss of function of this gene reduces the mobility of the cilia but we didn’t know if that was due to a direct or indirect effect of the mutation.’ Thanks to the functional analyses of gene CCDC39 the researchers succeeded in demonstrating that the components of the inner dynein arms and the dynein regulatory complex (DRC), an important intermediary of ciliary mobility, are linked to the expression of this gene. ‘The CCDC39 gene plays a key role in the assembly of the cilia’s internal structures, and its mutation affects the correct functioning of the inner dynein arms and the dynein regulatory complex,’ point out the researchers. It is in this way that people who have such mutations have a sort of rigidity in the fluttering of their vibrant cilia.
(1). Merveille AC, Davis EE, Becker-Heck A, Legendre M, Amirav I, Bataille G, Belmont J, Beydon N, Billen F, Clément A, Clercx C, Coste A, Crosbie R, de Blic J, Deleuze S, Duquesnoy P, Escalier D, Escudier E, Fliegauf M, Horvath J, Hill K, Jorissen M, Just J, Kispert A, Lathrop M, Loges NT, Marthin JK, Momozawa Y, Montantin G, Nielsen KG, Olbrich H, Papon JF, Rayet I, Roger G, Schmidts M, Tenreiro H, Towbin JA, Zelenika D, Zentgraf H, Georges M, Lequarré AS, Katsanis N, Omran H, Amselem S. CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs. Nature Genetics Volume: 43, Pages:72–78 (2011) |
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