title: Otitis media in a new mouse model for CHARGE syndrome with a deletion in the Chd7 gene.
abstract: Otitis media is a middle ear disease common in children under three years old. Otitis media can occur in normal individuals with no other symptoms or syndromes, but it is often seen in individuals clinically diagnosed with genetic diseases such as CHARGE syndrome, a complex genetic disease caused by mutation in the Chd7 gene and characterized by multiple birth defects. Although otitis media is common in human CHARGE syndrome patients, it has not been reported in mouse models of CHARGE syndrome. In this study, we report a mouse model with a spontaneous deletion mutation in the Chd7 gene and with chronic otitis media of early onset age accompanied by hearing loss. These mice also exhibit morphological alteration in the Eustachian tubes, dysregulation of epithelial proliferation, and decreased density of middle ear cilia. Gene expression profiling revealed up-regulation of Muc5ac, Muc5b and Tgf-β1 transcripts, the products of which are involved in mucin production and TGF pathway regulation. This is the first mouse model of CHARGE syndrome reported to show otitis media with effusion and it will be valuable for studying the etiology of otitis media and other symptoms in CHARGE syndrome.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University Hospitals of Cleveland, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.
authors.forename: Cong
authors.initials: C
authors.lastname: Tian
authors.forename: Heping
authors.initials: H
authors.lastname: Yu
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.forename: Fengchan
authors.initials: F
authors.lastname: Han
authors.forename: Ye
authors.initials: Y
authors.lastname: Zheng
authors.forename: Cynthia F
authors.initials: CF
authors.lastname: Bartels
authors.forename: Deborah
authors.initials: D
authors.lastname: Schelling
authors.forename: James E
authors.initials: JE
authors.lastname: Arnold
authors.forename: Peter C
authors.initials: PC
authors.lastname: Scacheri
authors.forename: Qing Yin
authors.initials: QY
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001483:Base Sequence; D058747:CHARGE Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D004432:Ear, Middle / Q000473:pathology; D005064:Eustachian Tube / Q000378:metabolism / Q000473:pathology; D005091:Exons; D020869:Gene Expression Profiling; D005838:Genotype; D034381:Hearing Loss / Q000209:etiology; D006579:Heterozygote; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009077:Mucins / Q000235:genetics / Q000378:metabolism; D010033:Otitis Media / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D017384:Sequence Deletion; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C507367:Chd7 protein, mouse; D004268:DNA-Binding Proteins; D009077:Mucins; D053773:Transforming Growth Factor beta1