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

被引：56

作者：

Lucas, Jane S. ^{[1
]}

Adam, Elizabeth C. ^{[1
]}

Goggin, Patricia M. ^{[1
]}

Jackson, Claire L. ^{[1
]}

Powles-Glover, Nicola ^{[2
]}

Patel, Saloni H. ^{[2
]}

Humphreys, James ^{[2
]}

Fray, Martin D. ^{[2
]}

Falconnet, Emilie ^{[4
]}

Blouin, Jean-Louis ^{[4
]}

Cheeseman, Michael T. ^{[2
]}

Bartoloni, Lucia ^{[3
,4
]}

Norris, Dominic P. ^{[2
]}

Lackie, Peter M. ^{[1
]}

机构：

[1] Univ Southampton Fac Med, Southampton Gen Hosp, Southampton NIHR Resp Biomed Res Unit, Primary Ciliary Dyskinesia Grp, Southampton SO16 6YD, Hants, England

[2] MRC Harwell, Harwell Sci & Innovat Campus, Didcot OX11 0RD, Oxon, England

[3] ULSS12 Veneziana, Dept Clin Pathol, Venice, Italy

[4] Univ Geneva, Dept Genet & Dev, Geneva, Switzerland

来源：

HUMAN MUTATION | 2012年 / 33卷 / 03期

基金：

英国生物技术与生命科学研究理事会;

关键词：

mouse and human; primary ciliary dyskinesia (model); Dnah11; Dnahc11; SITUS-INVERSUS; DNAH11; MUTATIONS; MALE-INFERTILITY; IMMOTILE CILIA; NODAL FLOW; DYSKINESIA; MICE; ULTRASTRUCTURE; HYDROCEPHALUS; HETEROTAXY;

D O I：

10.1002/humu.22001

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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. Hum Mutat 33:495503, 2012. (C) 2011 Wiley Periodicals, Inc.

引用

页码：495 / 503

页数：9

共 43 条

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