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

• Main Authors: Ahmed Salman, Samuel B. Hutton, Tutte Newall, Jennifer A. Scott, Helen L. Griffiths, Helena Lee, Diego Gomez-Nicola, Andrew J. Lotery, Jay E. Self
• Format: Article
• Language: English
• Published: MDPI AG 2020-09-01
• Series: Genes
• Subjects: nystagmus; Idiopathic Infantile Nystagmus; FRMD7; retina; optokinetic nystagmus
• Online Access: https://www.mdpi.com/2073-4425/11/10/1157

In this study, we seek to exclude other pathophysiological mechanisms by which <i>Frmd7</i> knock-down may cause Idiopathic Infantile Nystagmus (IIN) using the <i>Frmd7^.tm1a</i> and <i>Frmd7^.tm1b</i> murine models. We used a combination of genetic, histological and visual function techniques to characterize the role of <i>Frmd7</i> gene in IIN using a novel murine model for the disease. We demonstrate that the <i>Frmd7^.tm1b</i> allele represents a more robust model of <i>Frmd7</i> knock-out at the mRNA level. The expression of <i>Frmd7</i> was investigated using both antibody staining and X-gal staining confirming previous reports that <i>Frmd7</i> 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 <i>Frmd7</i> mutant models when compared with wild-type mice. High-speed eye-tracking recordings of <i>Frmd7</i> mutant mice confirm a specific horizontal optokinetic reflex defect. In summary, our study confirms the likely role for <i>Frmd7</i> in the optokinetic reflex in mice mediated by starburst amacrine cells. We show that the <i>Frmd7^.tm1b</i> model provides a more robust knock-out than the <i>Frmd7^.tm1a</i> 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 <i>Frmd7</i> is expressed, in the pathophysiology of IIN.