Loss of the chromatin remodeler CHD7 impacts glial cells and myelination in the mouse cochlear spiral ganglion.

Autor: Ritter KE; Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA., Lynch SM; College of Literature, Science and Art, University of Michigan, Ann Arbor, MI, USA., Gorris AM; College of Literature, Science and Art, University of Michigan, Ann Arbor, MI, USA., Beyer LA; Department of Otolaryngology - Head and Neck Surgery, University of Medical School, Ann Arbor, MI, USA., Kabara L; Department of Otolaryngology - Head and Neck Surgery, University of Medical School, Ann Arbor, MI, USA., Dolan DF; Department of Otolaryngology - Head and Neck Surgery, University of Medical School, Ann Arbor, MI, USA., Raphael Y; Department of Otolaryngology - Head and Neck Surgery, University of Medical School, Ann Arbor, MI, USA., Martin DM; Department of Pediatrics, University of Michigan Medical School, Ann Arbor, MI, USA; Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, USA. Electronic address: donnamm@med.umich.edu.
Jazyk: angličtina
Zdroj: Hearing research [Hear Res] 2022 Dec; Vol. 426, pp. 108633. Date of Electronic Publication: 2022 Oct 13.
DOI: 10.1016/j.heares.2022.108633
Abstrakt: CHARGE syndrome is a multiple anomaly developmental disorder characterized by a variety of sensory deficits, including sensorineural hearing loss of unknown etiology. Most cases of CHARGE are caused by heterozygous pathogenic variants in CHD7, the gene encoding Chromodomain DNA-binding Protein 7 (CHD7), a chromatin remodeler important for the development of neurons and glial cells. Previous studies in the Chd7 Gt/+ mouse model of CHARGE syndrome showed substantial neuron loss in the early stages of the developing inner ear that are compensated for by mid-gestation. In this study, we sought to determine if early developmental delays caused by Chd7 haploinsufficiency affect neurons, glial cells, and inner hair cell innervation in the mature cochlea. Analysis of auditory brainstem response recordings in Chd7 Gt/+ adult animals showed elevated thresholds at 4 kHz and 16 kHz, but no differences in ABR Wave I peak latency or amplitude compared to wild type controls. Proportions of neurons in the Chd7 Gt/+ adult spiral ganglion and densities of nerve projections from the spiral ganglion to the organ of Corti were not significantly different from wild type controls. Inner hair cell synapse formation also appeared unaffected in mature Chd7 Gt/+ cochleae. However, histological analysis of adult Chd7 Gt/+ cochleae revealed diminished satellite glial cells and hypermyelinated Type I spiral ganglion axons. We characterized the expression of CHD7 in developing inner ear glia and found CHD7 to be expressed during a tight window of inner ear development at the Schwann cell precursor stage at E9.5. While cochlear neurons appear to differentiate normally in the setting of Chd7 haploinsufficiency, our results suggest an important role for CHD7 in glial cells in the inner ear. This study highlights the dynamic nature of CHD7 activity during inner ear development in mice and contributes to understanding CHARGE syndrome pathology.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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