The effects of dystrophin gene mutations on the ERG in mice and humans

Abstract

Purpose: The authors' earlier findings of a negative electroretinogram (ERG) in a boy with Duchenne muscular dystrophy (DMD) led them to investigate dystrophin gene deletions and ERGs in five boys with DMD. The authors wanted to determined whether there were similar ERG findings in an animal model for DMD, the mdx mouse.

Methods: Ganzfeld ERGs were recorded in five boys with DMD after a complete ophthalmic examination. The dystrophin gene was analyzed by Southern blot hybridization. ERGs were recorded in anesthetized mdx and control mice with a modified Grass photostimulator (Grass Instrument Company, Quincy, MA).

Results: Ophthalmic examinations in all five boys had normal findings, yet an abnormal negative ERG was recorded for each subject. The subjects' gene deletions were variable, ranging from large deletions to no detectable deletions. The ERGs of the mdx mice were normal and did not differ significantly from those of the control mice.

Conclusions: The authors believe the unique ERG recorded for the human subjects is a manifestation of DMD associated with defects at the dystrophin gene locus and represents a new clinical entity. The ERG of the mdx mouse may be spared for several reasons, including milder effects of the mouse gene defect, differences in muscle and retinal gene product, or species differences in the biochemical role of dystrophin. The ERG shows promise of becoming a noninvasive diagnostic tool for DMD and its milder allelic forms.