CHD7 deficiency in "Looper", a new mouse model of CHARGE syndrome, results in ossicle malformation, otosclerosis and hearing impairment.
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.
Murdoch Childrens Research Institute, Parkville, Victoria, Australia.
Jacqueline M
JM
Ogier
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.
Marina R
MR
Carpinelli
ARC Centre of Excellence for Coherent X-ray Science, Department of Physics, La Trobe University, Bundoora, Victoria, Australia.
Benedicta D
BD
Arhatari
Department of Ophthalmology, Royal Melbourne Hospital, Parkville, Victoria, Australia.
R C Andrew
RC
Symons
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.
Benjamin T
BT
Kile
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.
Rachel A
RA
Burt
D000818:Animals; D058747:CHARGE Syndrome / Q000235:genetics / Q000503:physiopathology*; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D034381:Hearing Loss / Q000209:etiology / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010040:Otosclerosis / Q000209:etiology / Q000235:genetics*
C507367:Chd7 protein, mouse; D004268:DNA-Binding Proteins