title: Static respiratory cilia associated with mutations in Dnahc11/DNAH11: a mouse model of PCD.
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 Dnahc11(iv) 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 Dnahc11(iv) mouse is robust, lacks secondary defects, and requires no intervention to precipitate the phenotype. Together these findings show the Dnahc11(iv) 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.
authors.affiliation: Primary Ciliary Dyskinesia Group, Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Southampton, UK.
authors.forename: Jane S
authors.initials: JS
authors.lastname: Lucas
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Adam
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Goggin
authors.forename: Claire L
authors.initials: CL
authors.lastname: Jackson
authors.forename: Nicola
authors.initials: N
authors.lastname: Powles-Glover
authors.forename: Saloni H
authors.initials: SH
authors.lastname: Patel
authors.forename: James
authors.initials: J
authors.lastname: Humphreys
authors.forename: Martin D
authors.initials: MD
authors.lastname: Fray
authors.forename: Emilie
authors.initials: E
authors.lastname: Falconnet
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Blouin
authors.forename: Michael T
authors.initials: MT
authors.lastname: Cheeseman
authors.forename: Lucia
authors.initials: L
authors.lastname: Bartoloni
authors.forename: Dominic P
authors.initials: DP
authors.lastname: Norris
authors.forename: Peter M
authors.initials: PM
authors.lastname: Lackie
mesh_terms: D000818:Animals; D056444:Axonemal Dyneins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007619:Kartagener Syndrome / Q000235:genetics*; D008297:Male; D051379:Mice; D009154:Mutation
chemical_list: C402391:Dnah11 protein, mouse; D056444:Axonemal Dyneins