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Otitis media in a new mouse model for CHARGE syndrome with a deletion in the Chd7 gene
Cong Tian1, Heping Yu, Bin Yang
1Department of Otolaryngology-Head and Neck Surgery, University Hospitals of Cleveland, Case Western Reserve University School of Medicine, Cleveland, Ohio, United States of America.
Insights
A new mouse model with a Chd7 gene mutation develops chronic otitis media and hearing loss, offering insights into CHARGE syndrome. This model aids research into middle ear disease and associated genetic conditions.
Area of Science:
- Genetics
- Otolaryngology
- Developmental Biology
Background:
- Otitis media (middle ear infection) is prevalent in young children.
- CHARGE syndrome, a genetic disorder from Chd7 gene mutations, is linked to otitis media in humans.
- Existing mouse models of CHARGE syndrome have not exhibited otitis media.
Purpose of the Study:
- To establish and characterize a novel mouse model for CHARGE syndrome exhibiting otitis media.
- To investigate the pathological mechanisms underlying otitis media in this genetic context.
Main Methods:
- Generated a mouse model with a spontaneous deletion mutation in the Chd7 gene.
- Performed morphological analysis of the middle ear and Eustachian tubes.
- Conducted gene expression profiling to identify molecular changes.
Main Results:
- The Chd7 mutant mice developed chronic otitis media with early onset and associated hearing loss.
- Observed Eustachian tube malformations, altered epithelial cell proliferation, and reduced cilia density.
- Detected increased expression of Muc5ac, Muc5b, and Tgf-β1, indicating mucin production and TGF pathway involvement.
Conclusions:
- This study presents the first mouse model of CHARGE syndrome with otitis media with effusion.
- The model provides a valuable tool for understanding the pathogenesis of otitis media in CHARGE syndrome.
- Further research can utilize this model to explore therapeutic strategies for CHARGE syndrome-related symptoms.
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.
