Abstract
Macaca fascicularis is a highly advantageous model in which to study human cochlea with regard to both evolutionary proximity and physiological similarity of the auditory system. To better understand the properties of primate cochlear function, we analyzed the genes predominantly expressed in M. fascicularis cochlea. We compared the cochlear transcripts obtained from an adult male M. fascicularis by macaque and human GeneChip microarrays with those in multiple macaque and human tissues or cells and identified 344 genes with expression levels more than 2-fold greater than in the other tissues. These “cochlear signature genes” included 35 genes responsible for syndromic or nonsyndromic hereditary hearing loss. Gene set enrichment analysis revealed groups of genes categorized as “ear development” and “ear morphogenesis” in the top 20 gene ontology categories in the macaque and human arrays, respectively. This dataset will facilitate both the study of genes that contribute to primate cochlear function and provide insight to discover novel genes associated with hereditary hearing loss that have yet to be established using animal models.
Highlights
The basic histological components of cochlear tissues are consistent among mammalian species[1], each species has a unique range of auditory frequencies[2] to perceive environmental change and communicate
Gene expression analysis from postmortem, formalin-fixed human cochlea is challenging due to fragmentation of the nucleic acids during fixation followed by decalcification and paraffin-embedding[8], would provide limited information for biomedical research
While affinities of the probes on the human array to the transcripts in the macaque tissues seemed not identical to those on macaque array[5], the transcripts between human and M. fascicularis show more than 95% identity[3], suggesting that profiles of gene expression in macaque cochleae can be analyzed on human array platforms in substitution
Summary
The basic histological components of cochlear tissues are consistent among mammalian species[1], each species has a unique range of auditory frequencies[2] to perceive environmental change and communicate. This physiological variation can be explained by the morphological properties of conductive auditory organs such as the auditory canal, eardrum, and ear ossicles and by the magnitude of expression of cochlea-specific genes. The extremely high similarity between human transcripts and those of M. fascicularis as well as Macaca mulatta (rhesus macaque) has enabled investigators to study the gene expression profiles of macaque tissues using both the macaque and human microarray platforms[5]. We sought to generate the profile of genes predominantly expressed in freshly-dissected whole cochlear tissue of M. fascicularis, which should include genes critical to cochlear function
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