@article {1635653,
	title = {Early disruption of photoreceptor cell architecture and loss of vision in a humanized pig model of usher syndromes},
	journal = {EMBO Mol Med},
	volume = {14},
	number = {4},
	year = {2022},
	month = {2022 Apr 07},
	pages = {e14817},
	abstract = {Usher syndrome (USH) is the most common form of monogenic deaf-blindness. Loss of vision is untreatable and there are no suitable animal models for testing therapeutic strategies of the ocular constituent of USH, so far. 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. Fibroblasts from USH1C pigs or USH1C patients showed significantly elongated primary cilia, confirming USH as a true and general ciliopathy. Primary cells also proved their capacity for assessing the therapeutic potential of CRISPR/Cas-mediated gene repair or gene therapy in\&nbsp;vitro. AAV-based delivery of harmonin into the eye of USH1C pigs indicated therapeutic efficacy in\&nbsp;vivo.},
	keywords = {Animals, Cell Cycle Proteins, Cytoskeletal Proteins, Humans, Photoreceptor Cells, Swine, Usher Syndromes},
	issn = {1757-4684},
	doi = {10.15252/emmm.202114817},
	author = {Grotz, Sophia and Sch{\"a}fer, Jessica and Wunderlich, Kirsten A and Ellederova, Zdenka and Auch, Hannah and B{\"a}hr, Andrea and Runa-Vochozkova, Petra and Fadl, Janet and Arnold, Vanessa and Ardan, Taras and Veith, Miroslav and Santamaria, Gianluca and Dhom, Georg and Hitzl, Wolfgang and Kessler, Barbara and Eckardt, Christian and Klein, Joshua and Brymova, Anna and Linnert, Joshua and Kurome, Mayuko and Zakharchenko, Valeri and Fischer, Andrea and Blutke, Andreas and D{\"o}ring, Anna and Suchankova, Stepanka and Popelar, Jiri and Rodr{\'\i}guez-Bocanegra, Eduardo and Dlugaiczyk, Julia and Straka, Hans and May-Simera, Helen and Wang, Weiwei and Laugwitz, Karl-Ludwig and Vandenberghe, Luk H and Wolf, Eckhard and Nagel-Wolfrum, Kerstin and Peters, Tobias and Motlik, Jan and Fischer, M Dominik and Wolfrum, Uwe and Klymiuk, Nikolai}
}
