TY - JOUR T1 - Early Disruption of Photoreceptor Cell Architecture and Loss of Vision in a Humanized Pig Model of Usher Syndrome JF - bioRxiv DO - 10.1101/2021.05.31.446123 SP - 2021.05.31.446123 AU - Sophia Grotz AU - Jessica Schäfer AU - Kirsten A. Wunderlich AU - Zdenka Ellederova AU - Hannah Auch AU - Andrea Bähr AU - Petra Runa-Vochozkova AU - Janet Plutniok AU - Vanessa Arnold AU - Taras Ardan AU - Miroslav Veith AU - Gianluca Santamaria AU - Georg Dhom AU - Wolfgang Hitzl AU - Barbara Kessler AU - Mayuko Kurome AU - Valeri Zakharchenko AU - Joshua Linnert AU - Andrea Fischer AU - Andreas Blutke AU - Anna Döring AU - Stepanka Suchankova AU - Jiri Popelar AU - Helen May-Simera AU - Karl-Ludwig Laugwitz AU - Luk H. Vandenberghe AU - Eckhard Wolf AU - Kerstin Nagel-Wolfrum AU - Jan Motlik AU - M. Dominik Fischer AU - Uwe Wolfrum AU - Nikolai Klymiuk Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/05/31/2021.05.31.446123.abstract N2 - Usher syndrome (USH) is the most common form of monogenic deaf-blindness. Loss of vision is untreatable and, so far, there are no suitable animal models for testing therapeutic strategies. By introducing a human mutation into the harmonin-encoding USH1C gene in pigs, we generated the first translational animal model for USH type 1 with characteristic hearing defect, vestibular dysfunction and visual impairment. Changes in photoreceptor architecture, quantitative motion analysis and electroretinography were characteristics of the reduced retinal virtue in USH1C pigs. Primary cells from those animals and USH1C patients showed significantly elongated primary cilia, compared to wild-type, confirming the nature of USH as a true and general ciliopathy and proving the therapeutic capacity of gene supplementation and gene repair approaches.Competing Interest StatementThe authors have declared no competing interest. ER -