[International expert consensus on gene therapy for hereditary hearing loss: based on clinical trials].
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Journal Article↗
Biomedical subjects
Zheng-Yi Chen
Publications and source records attributed to Zheng-Yi Chen.
Understanding inner ear development with gene expression profiling.
Understanding the development of the inner ear requires knowing the spatial and temporal pattern of gene expression, and the functions of those gene products. In the last decade, hearing research has benefited tremendously from the progress of the human and mouse genome projects, as amply illustrated by the identification of many deafness genes in both human and mouse. However, the sheer amount of information generated from the genome project has far outpaced the rate at which it is utilized. Microarray technology offers a means to quantify the expression level of transcripts at a whole-genome scale. Cross-tissue comparisons will identify genes unique to the inner ear, which will expedite the identification of new deafness genes. Microdissection and subtraction after ablation of cell types can reveal genes expressed in certain cells, such as hair cells. Expression profiling of both inner ear and other tissues, under a variety of conditions (such as during development, with drug treatment or in knock-out animals), can be used for cluster analysis to group genes of similar expression. Coexpression can suggest functional pathways and interactions between known genes, and can identify new genes in a structure or pathway. In this review we give examples for both transcription factors and cochlear structures.
Animals↗
Vascular defects and sensorineural deafness in a mouse model of Norrie disease.
Norrie disease is an X-linked recessive syndrome of blindness, deafness, and mental retardation. A knock-out mouse model with an Ndp gene disruption was studied. We examined the hearing phenotype, including audiological, histological, and vascular evaluations. As is seen in humans, the mice had progressive hearing loss leading to profound deafness. The primary lesion was localized to the stria vascularis, which houses the main vasculature of the cochlea. Fluorescent dyes showed an abnormal vasculature in this region and eventual loss of two-thirds of the vessels. We propose that one of the principal functions of norrin in the ear is to regulate the interaction of the cochlea with its vasculature.
Acoustic Stimulation↗
An inner ear gene expression database.
Microarray technology has provided an unprecedented opportunity to study gene expression profiles at a whole-genome level. As a first step toward a comprehensive understanding of inner ear gene expression, mouse cochleas were examined at two developmental stages (P2 and P32) using GeneChip oligonucleotide arrays. A large number of genes and ESTs (> 10,000) were found to be expressed in the cochlea. Expression profiles derived from duplicate samples at the same developmental stages showed general agreement and indicated the reproducibility of the assay. The expression of many known hair-cell genes was detected in the whole-cochlea samples, demonstrating the relatively high sensitivity of the assay. Genes highly expressed only at P2 or P32 were also identified and their expression patterns correlate with their functions in the cochlea. A web-based database with external links was set up for public access, which should facilitate the discovery of genes important in the development and function of the inner ear and should aid the identification of additional deafness genes.
Animals↗