Identification and characterisation of a new gene that is mutated in an autosomal recessive form of nonsyndromic hearing impairment

• Applicant: Dr. Guntram Borck
• Subject Area: Human Genetics
• Term: from 2008 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 91925471

The aim of my previous DFG research proposal entitled “Identification and characterisation of a new gene that is mutated in an autosomal recessive form of nonsyndromic hearing impairment“ was to find and initially characterize a novel gene which is mutated in an autosomal-recessive form of hearing impairment, called DFNB42. During the 2009/2010 funding period of this DFG grant I have identified mutations of the ILDR1 gene as causative for hearing impairment at the DFNB42 locus. Thus, ILDR1 is a novel deafness gene. The results of this study have been published in the January 2011 issue of the Amercian Journal of Human Genetics. In the 2 years of follow-up for which I present the grant application here, I plan to better characterize the role that ILDR1 plays in the inner ear and in the pysiological hearing process. ILDR1 encodes a putative transmembrane receptor of unknown function. We have previously shown by mRNA in situ hybridization that the mouse ortholog Ildr1 is expressed in hair cells and supporting cells of the cochlea and in hair cells of the vestibular organ. I plan to extend these results by pecisely localizing the Ildr1 protein in the mouse inner ear by immunochemistry. Moreover, I will search for ILDR1 ligands and interaction partners by using novel methods of protein biochemistry by which interaction partners can be identified not only for cytosolic but also for transmembrane proteins. Finally, I plan to create a first animal model for DFNB42 by knocking down the expression of ILDR1 paralogs in the model organism, zebrafish, which will allow for a better understanding of the the contribution of ILDR1 to hearing in vertebrates. These analyses will hopefully contribute to a better understanding of the role that ILDR1 plays in hearing and deafness and more generally to a deeper understanding of the complex process of hearing itself.

• DFG Programme: Research Grants