In this issue
Looks normal, but may not function properly: A “new” mouse model for primary ciliary dyskinesia
Article first published online: 14 FEB 2012
© 2012 Wiley Periodicals, Inc.
Volume 33, Issue 3, page 5, March 2012
How to Cite
Qi, M. (2012), Looks normal, but may not function properly: A “new” mouse model for primary ciliary dyskinesia. Hum. Mutat., 33: 5. doi: 10.1002/humu.22570
- Issue published online: 14 FEB 2012
- Article first published online: 14 FEB 2012
In our daily life, we quite often encounter people or things that are not really doing the jobs that they appear to be doing. To be able to similarly identify a part of the body that appears normal but is not functioning properly is critical in clinical practice. In this issue, Lucas et al. (Hum Mutat 33:495–503, 2012) provide an excellent example through their search for a mouse model of the human inherited disease primary ciliary dyskinesia (PCD). PCD is a genetically heterogeneous, autosomal recessive disorder characterized by chronic respiratory tract infection and impaired fertility. About half of PCD patients have their thorax and abdomen in reversed or mirrored positions (inversus viscerum). Lucas and colleagues carefully restudied a classical inversus viscerum mouse (Dnahc11iv) identified over 50 years ago. The mouse had a mutation in the Dnahc11 locus, which encodes dynein axonemal heavy chain 11 (encoded by the DNAH11 gene in humans). They found that, although the trachial cilia ultrastructure was normal in the mouse, they were actually immotile. Sperm also had reduced motility. With this in mind, they tested two PCD patients with normal ultrastructure but static cilia, and indeed found mutations in DNAH11 previously found in PCD patients with hyperkinetic cilia.
The careful functional and microstructural analysis performed by the authors lead to a new molecular diagnosis and allowed them to draw a connection between a known human disease and what proved to be a “new” mouse model for a disease. This example should rekindle interest in examining other potential animal models for human disease, which may not have been as carefully studied in the past as we assume they were.