SOX9 and SOX10 control fluid homeostasis in the inner ear for hearing through independent and cooperative mechanisms.

ABSTRACT: The in vivo mechanisms underlying dominant syndromes caused by mutations in SRY-Box Transcription Factor 9 (SOX9) and SOX10 (SOXE) transcription factors, when they either are expressed alone or are coexpressed, are ill-defined. We created a mouse model for the campomelic dysplasia SOX9^Y440X mutation, which truncates the transactivation domain but leaves DNA binding and dimerization intact. Here, we find that SOX9^Y440X causes deafness via distinct mechanisms in the endolymphatic sac (ES)/duct and cochlea. By contrast, conditional heterozygous Sox9-null mice are normal. During the ES development of Sox9^Y440X/+ heterozygotes, Sox10 and genes important for ionic homeostasis are down-regulated, and there is

SUBMITTER: Szeto IYY 

PROVIDER: S-EPMC9674217 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature