CHD7 deficiency in "Looper", a new mouse model of CHARGE syndrome, results in ossicle malformation, otosclerosis and hearing impairment

Jacqueline M Ogier; Marina R Carpinelli; Benedicta D Arhatari; R C Andrew Symons; Benjamin T Kile; Rachel A Burt

doi:10.1371/journal.pone.0097559

CHD7 deficiency in "Looper", a new mouse model of CHARGE syndrome, results in ossicle malformation, otosclerosis and hearing impairment

PLoS One. 2014 May 19;9(5):e97559. doi: 10.1371/journal.pone.0097559. eCollection 2014.

Authors

Jacqueline M Ogier¹, Marina R Carpinelli², Benedicta D Arhatari³, R C Andrew Symons⁴, Benjamin T Kile⁵, Rachel A Burt⁶

Affiliations

¹ Murdoch Childrens Research Institute, Parkville, Victoria, Australia.
² Murdoch Childrens Research Institute, Parkville, Victoria, Australia; The HEARing Cooperative Research Centre, Parkville, Victoria, Australia; Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
³ ARC Centre of Excellence for Coherent X-ray Science, Department of Physics, La Trobe University, Bundoora, Victoria, Australia.
⁴ Department of Ophthalmology, Royal Melbourne Hospital, Parkville, Victoria, Australia.
⁵ Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia; Department of Genetics, University of Melbourne, Parkville, Victoria, Australia.
⁶ Murdoch Childrens Research Institute, Parkville, Victoria, Australia; The HEARing Cooperative Research Centre, Parkville, Victoria, Australia; Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia; Department of Genetics, University of Melbourne, Parkville, Victoria, Australia; Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia.

Abstract

CHARGE syndrome is a rare human disorder caused by mutations in the gene encoding chromodomain helicase DNA binding protein 7 (CHD7). Characteristics of CHARGE are varied and include developmental ear and hearing anomalies. Here we report a novel mouse model of CHD7 dysfunction, termed Looper. The Looper strain harbours a nonsense mutation (c.5690C>A, p.S1897X) within the Chd7 gene. Looper mice exhibit many of the clinical features of the human syndrome, consistent with previously reported CHARGE models, including growth retardation, facial asymmetry, vestibular defects, eye anomalies, hyperactivity, ossicle malformation, hearing loss and vestibular dysfunction. Looper mice display an otosclerosis-like fusion of the stapes footplate to the cochlear oval window and blepharoconjunctivitis but not coloboma. Looper mice are hyperactive and have vestibular dysfunction but do not display motor impairment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
CHARGE Syndrome / genetics
CHARGE Syndrome / physiopathology*
DNA-Binding Proteins / deficiency*
DNA-Binding Proteins / genetics
Hearing Loss / etiology
Hearing Loss / genetics*
Humans
Male
Mice
Mice, Inbred BALB C
Otosclerosis / etiology
Otosclerosis / genetics*

Substances

Chd7 protein, mouse
DNA-Binding Proteins

Grants and funding

This work was supported by the HEARing CRC, established and supported under the Cooperative Research Centres Program – an Australian Government Initiative; the Garnett Passe and Rodney Williams Memorial Foundation (fellowship to MRC); the Australian Government’s National Health and Medical Research Council (Program Grants 461219 and 1016647, and a fellowship to BTK); the Sylvia and Charles Viertel Foundation (fellowship to BTK); the Victorian State Government’s Operational Infrastructure Support Program; the Australian Government’s NHMRC IRIISS; and a National Collaborative Research Infrastructure Strategy grant to the Australian Phenomics Network. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.