Heterozygous B6;C3‐Opa1Q285STOP mouse model of dominant optic atrophy displays subtle neuromuscular features with age

Abstract Purpose OPA1 autosomal dominant optic atrophy is a slowly progressive optic neuropathy. A neurological ‘plus’ phenotype has been reported with some OPA1 mutations, prompting further systemic evaluation of our mouse model. Heterozygous Opa1 mutant mice (B6;C3‐Opa1Q285STOP), with documented visual defects on optokinetic drum tracking and optic nerve defects on electron microscopy, were assessed. Here we explore neuromuscular aspects of the phenotype. Methods Published husbandry and genotyping protocols were used. Body weight, SHIRPA test, accelerating rotarod and visual acuity testing using the optokinetic drum was carried out. Results Mean weights of all Opa1 male and female mice over 6 months age showed a trend towards lighter weight in Opa1+/‐ mice (WT 32.74g, SD=6.0; Het 29.47g, SD=2.7 ; p> 0.05). By 20 months of age there was a statistically significant difference between WT and Hets (WT 40.6g, SD=3.1; Het 28.77g, SD=2.44; p< 0.05). SHIRPA neurological screen of 12 month old animals showed that Opa1+/‐ (Hets) were less active than wild type (WT) in an open arena (p<0.05), and less able to perform the wire hang test (p<0.05). 12 month Opa1+/‐ showed reduced mean performance on rotarod (WT 92s, SD=10; Het 70s, SD=20.9; p=0.05). Rotarod testing at 20 months was discontinued since grossly obese wild type mice were unable to perform the test and act as controls. Conclusion Opa1+/‐ mice are lighter than WT age and sex matched controls. Rotarod testing confirms a subtle neuromuscular defect in Opa1+/‐ mice in line with neurological (SHIRPA) testing.