Visual electrophysiological features of two naturally occurring mouse models with retinal dysfunction

Area of Science:

• Genetics
• Ophthalmology
• Animal Models

Background:

• Inherited retinal disorders (IRDs) represent a significant cause of vision loss.
• Developing animal models is crucial for understanding IRD pathogenesis and testing therapies.
• Spontaneous mutations in mice offer unique opportunities to study novel genetic causes of retinal dysfunction.

Purpose of the Study:

• To characterize the functional and structural features of two novel mouse strains, IRD1 and IRD2, with spontaneous retinal dysfunction.
• To elucidate the genetic basis and inheritance patterns of the observed retinal phenotypes.

Main Methods:

• Scotopic and photopic electroretinograms (ERGs) were performed on IRD1 and IRD2 mice at 1 month of age.
• Retinal histology was assessed using light microscopy at 1 and 3 months of age.
• Mating studies, including backcrosses and F1 crosses, were conducted to determine inheritance patterns and genetic relationships.

Main Results:

• IRD1 mice displayed both scotopic and photopic ERG abnormalities, while IRD2 mice showed affected scotopic but normal photopic ERGs.
• Retinal structures remained normal in both IRD1 and IRD2 mice up to 3 months of age.
• Both IRD1 and IRD2 phenotypes followed an autosomal recessive inheritance pattern, with F1 offspring exhibiting the IRD2 (rod dysfunction) phenotype.

Conclusions:

• IRD1 and IRD2 mice possess mutations in distinct rod function-related genes, with IRD1 additionally having a mutation in a cone function-related gene.
• These novel mouse models exhibit significant retinal dysfunction without apparent anatomical changes, making them valuable for studying human inherited retinal disorders.
• The identified genetic mutations and resulting phenotypes provide new insights into the molecular mechanisms underlying inherited retinal diseases.