The eye screen of the German Mouse Clinic (GMC) ‐ New genetic insights into eye development and ocular disorders

Abstract

AbstractPurpose To summarize GMC ‐ Eye Screen findings with about 350 tested mouse mutant lines.Methods Eye morphology was analyzed by Slit Lamp Biomicroscopy/Scheimpflug Imaging and Ophthalmoscopy/Optical Coherence Tomography, eye size by Laser Interference Biometry, and the Virtual Optokinetic Drum was used for testing visual ability.Results The GMC is a large‐scale phenotyping center where mouse models for human diseases are analyzed in a standardized way. More than 550 parameters are investigated in 14 different areas including behavior, neurology, cardiovascular functionality and vision and eye development. In the past 12 years, we identified eye pathologies in 43 mutant lines of the GMC workflow. The majority of them exhibited irregular eye sizes (72%), followed by morphological changes as corneal and lens opacities (21%) or retinal damages (16%) and moderately reduced visual abilities (7%). Overall phenotype predictions (EuroPhenome database; http://www.europhenome.org/) indicated that 89% of these lines were additionally affected in behavioral and/or neurological parameters, pointing to general relations between eye and brain development. Moreover, 46% showed heart impairments, connecting eye diseases with cardiovascular risks. Our data further proved for 11 gene products a previously unknown participation in ocular processes. These include the chromatin modifiers Asxl1 and Mysm1, the transcription factor Nfya as well as Arvcf, Jmjd5 and Slc20a2 with a role in cell‐cell communication, protein hydroxylation and phosphate transport, respectively.Conclusion The GMC ‐ Eye Screen is an effective approach for improving knowledge about ocular genetics and detecting associations with non‐ocular disorders.