Static respiratory cilia associated with mutations in Dnahc11/DNAH11: a mouse model of PCD

Lucas, Jane S., Adam, Elizabeth C., Goggin, Patricia M., Jackson, Claire L., Powles-Glover, Nicola, Patel, Saloni H, Humphreys, James, Fray, Martin D., Falconnet, Emilie, Blouin, Jean-Louis, Cheeseman, Michael T., Bartoloni, Lucia, Norris, Dominic P. and Lackie, Peter M. (2012) Static respiratory cilia associated with mutations in Dnahc11/DNAH11: a mouse model of PCD. Human Mutation, 33 (3), 495-503. (doi:10.1002/humu.22001). (PMID:22102620)

Abstract

Primary ciliary dyskinesia (PCD) is an inherited disorder causing significant upper and lower respiratory tract morbidity and impaired fertility. Half of PCD patients show abnormal situs. Human disease loci have been identified but a mouse model without additional deleterious defects is elusive. The inversus viscerum mouse,mutated at the outer arm dynein heavy chain 11 locus (Dnahc11) is a known model of heterotaxy. We demonstrated immotile tracheal cilia with normal ultrastructure and reduced sperm motility in the Dnahc11iv mouse. This is accompanied by gross rhinitis, sinusitis and otitis media, all indicators of human PCD. Strikingly, age related progression of the disease is evident. The Dnahc11iv mouse is robust, lacks secondary defects and requires no intervention to precipitate the phenotype. Together these findings show the Dnahc11iv mouse to be an excellent model of many aspects of human PCD. Mutation of the homologous human locus has previously been associated with hyperkinetic tracheal cilia in PCD. Two PCD patients with normal ciliary ultrastructure, one with immotile and one with hyperkinetic cilia were found to carry DNAH11 mutations. Three novel DNAH11 mutations were detected indicating that this gene should be investigated in patients with normal ciliary ultrastructure and static, as well as hyperkinetic cilia.

This record has no associated files available for download.

Contributors

Author: Jane S. Lucas

Author: Peter M. Lackie

Download statistics