Characterization of the Frmd7 Knock-Out Mice Generated by the EUCOMM/COMP Repository As a Model for Idiopathic Infantile Nystagmus (IIN)

In this study, we seek to exclude other pathophysiological mechanisms by which knock-down may cause Idiopathic Infantile Nystagmus (IIN) using the and murine models. We used a combination of genetic, histological and visual function techniques to characterize the role of gene in IIN using a novel murine model for the disease. We demonstrate that the allele represents a more robust model of knock-out at the mRNA level. The expression of was investigated using both antibody staining and X-gal staining confirming previous reports that expression in the retina is restricted to starburst amacrine cells and demonstrating that X-gal staining recapitulates the expression pattern in this model. Thus, it offers a useful tool for further expression studies. We also show that gross retinal morphology and electrophysiology are unchanged in these mutant models when compared with wild-type mice. High-speed eye-tracking recordings of mutant mice confirm a specific horizontal optokinetic reflex defect. In summary, our study confirms the likely role for in the optokinetic reflex in mice mediated by starburst amacrine cells. We show that the model provides a more robust knock-out than the model at the mRNA level, although the functional consequence is unchanged. Finally, we establish a robust eye-tracking technique in mice that can be used in a variety of future studies using this model and others. Although our data highlight a deficit in the optiokinetic reflex as a result of the starburst amacrine cells in the retina, this does not rule out the involvement of other cells, in the brain or the retina where is expressed, in the pathophysiology of IIN.