Johannes Gutenberg University Mainz

For over 25 years, the research group led by Professor Uwe Wolfrum of the Institute of Molecular Physiology at Johannes Gutenberg University Mainz (JGU) has been conducting research into Usher syndrome. 

Kerstin and Uwe Wolfrum have developed a pig model for USH1B. The researchers currently analyze a naturally occurring USH1B/MYO7A pig model bearing a biallelic nonsense mutation (p.Q181*) in the MYO7A gene. This project is in close collaboration with Michael Wendt, Hanover, and Doris Höltig, Berlin. They will make use of this model to define the mechanisms underlying the visual dysfunction in USH1B and to provide a large animal for preclinical evaluation of therapies for USH1B patients. Kerstin and Uwe Wolfrum are also working on a USH1C pig model.

Create a Nonhuman Pig Model of USH1C

Kerstin and Uwe Wolfrum and their teams have developed a transgenic USH1C pig model and investigated translational read-through inducing drugs in mouse and pig models with USH1C (p.R31X). This approach could serve as a treatment option for nonsense mutations in inherited retinal diseases.

Unraveling the retinal function of harmonin - USH1C

The USH1C/harmonin is a scaffold protein consisting of one harmonin homology, three PDZ, coiled-coil, and one proline-serine-threonine-rich (PST) domain through which numerous proteins including all other USH proteins bind. Extensive alternative splicing modulates harmonin´s modular composition and thus its molecular function in the cell. In the retina, specific harmonin isoforms are expressed in the photoreceptor cells and Müller glia cells where they are localized in the photosensitive outer segments, calyceal processes, synapses and in adhesions complexes, respectively. The researchers study harmonin´s functions in vitro and in cells, e.g., cells derived from patients or animal models and in vivo in our USH1C pig model.

Johannes Gutenberg University Mainz Science News