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

Static respiratory cilia associated with mutations in Dnahc11/DNAH11: a mouse model of PCD
Static respiratory cilia associated with mutations in Dnahc11/DNAH11: a mouse model of PCD
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.
1059-7794
495-503
Lucas, Jane S.
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Adam, Elizabeth C.
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Goggin, Patricia M.
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Jackson, Claire L.
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Powles-Glover, Nicola
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Patel, Saloni H
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Humphreys, James
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Fray, Martin D.
d75da42b-3a91-40fa-a7bb-f1d8bb3e4702
Falconnet, Emilie
ec9c9fca-a4ea-4727-ad2e-6e1725c49256
Blouin, Jean-Louis
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Cheeseman, Michael T.
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Bartoloni, Lucia
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Norris, Dominic P.
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Lackie, Peter M.
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Lucas, Jane S.
5cb3546c-87b2-4e59-af48-402076e25313
Adam, Elizabeth C.
8a62ff00-e6af-4859-be1f-fb36fa5f8d8d
Goggin, Patricia M.
44bfa939-e14e-48da-b91b-e74c5c747143
Jackson, Claire L.
ca0c242e-3638-4949-a0cb-f41e36067b8f
Powles-Glover, Nicola
f2b35b06-058a-422a-8501-df0abfed3e31
Patel, Saloni H
4e4fff0e-acb8-44ca-a718-d913c6a4d154
Humphreys, James
5a0ad6e9-2466-48ed-ae5b-2b0a349eaa75
Fray, Martin D.
d75da42b-3a91-40fa-a7bb-f1d8bb3e4702
Falconnet, Emilie
ec9c9fca-a4ea-4727-ad2e-6e1725c49256
Blouin, Jean-Louis
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Cheeseman, Michael T.
0b174fd4-8e26-4148-a179-e7381775044e
Bartoloni, Lucia
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Norris, Dominic P.
14b7f8e4-162c-4218-be30-8396224464d1
Lackie, Peter M.
4afbbe1a-22a6-4ceb-8cad-f3696dc43a7a

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)

Record type: Article

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.

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Published date: March 2012
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 203977
URI: http://eprints.soton.ac.uk/id/eprint/203977
ISSN: 1059-7794
PURE UUID: afc7b8ea-10ee-4906-8bab-10966c0e6bd3
ORCID for Jane S. Lucas: ORCID iD orcid.org/0000-0001-8701-9975
ORCID for Peter M. Lackie: ORCID iD orcid.org/0000-0001-7138-3764

Catalogue record

Date deposited: 22 Nov 2011 14:09
Last modified: 15 Mar 2024 03:12

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Contributors

Author: Jane S. Lucas ORCID iD
Author: Elizabeth C. Adam
Author: Patricia M. Goggin
Author: Claire L. Jackson
Author: Nicola Powles-Glover
Author: Saloni H Patel
Author: James Humphreys
Author: Martin D. Fray
Author: Emilie Falconnet
Author: Jean-Louis Blouin
Author: Michael T. Cheeseman
Author: Lucia Bartoloni
Author: Dominic P. Norris
Author: Peter M. Lackie ORCID iD

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