A specific promoter of the sensory cells of the inner ear defined by transgenesis

To date, no promoter sequence specific to the inner ear sensory cells (hair cells) has been reported. In an effort to understand the molecular mechani sms that determine hair cell fate in the inner ear, and with the goal of de veloping a valuable tool for gene therapy and for the generation of conditi onal knockouts, we initiated a search for cis-acting DNA sequences that reg ulate the expression of the murine Myo7a and human MYO7A genes. These genes encode the unconventional myosin VIIA which is expressed in hair cells and in some other epithelial cells. We generated lines of transgenic mice expr essing the green fluorescent protein (GFP) reporter gene under the control of several 5 ' -truncated versions of the Myo7a/MYO7A promoter region and i ntron 1. We obtained transgenic mice with a GFP expression restricted to th e hair cells of the inner ear, cochlea and vestibule. Successive deletions of the promoter allowed us to define a minimal sequence of 118 bp that is s ufficient, in the presence of intron 1, to target the transgene expression to hair cells. In addition, the deletion of intron 1 from the transgenes ab olished hair cell expression, thus indicating the presence of a strong enha ncer in the intron. This is the first report of regulatory sequences suffic ient to target the expression of a gene exclusively in sensory cells of the inner ear. It also opens up the possibility for the analysis of the hair c ell transcriptome.