High resolution magnetic resonance imaging of the brain in the dy/dy mouse with merosin-deficient congenital muscular dystrophy

Abstract

Magnetic resonance imaging (MRI) abnormalities in the cerebral white matter are a consistent feature of merosin-deficient human congenital muscular dystrophy, a disease caused by a primary defect in the expression of the laminin alpha2 chain of merosin. To investigate the relationship between imaging changes and merosin deficiency we undertook a MRI study in the dy/dy mouse, an animal model for this form of human congenital muscular dystrophy. High resolution in vivo imaging was performed on anaesthetized animals (two homozygous dy/dy mutants and two heterozygous dy/DY controls, aged 2.5 months) in a dedicated 11.7T magnetic resonance imaging scanner. T(1) and T(2) weighted images were normal in all mice and white matter changes were not seen at a stage of maturity when MRI changes are already very striking in human patients. Cerebral MRI abnormalities do not appear to be a feature of dy/dy mice, despite the virtual absence of merosin expression in the dy/dy mouse brain. Possible causes for this absence of MRI changes, and implications for the pathogenesis of the MRI changes in humans are reviewed.