Magnetic resonance imaging (MRI), pathologic examinations, and biochemical analyses were performed on 2 different canine mutants with
GM1 gangliosidosis (i.e., English Springer Spaniel and Portuguese Water Dog) and on age- and sex-matched controls. Serial MRI studies were also performed on a child with infantile-onset
GM1 gangliosidosis. The affected dogs had abnormalities on MRI, including a relative increase in gray matter and an abnormal signal intensity of cerebral and cerebellar white matter observed on T2-weighted MRI. White matter changes on MRI were similar to white matter abnormalities observed in a 15-month-old boy with
GM1 gangliosidosis. The weight ratio of white to gray matter from the frontal lobe was markedly reduced. Microscopic examination revealed characteristic ballooned neurons which stained lightly with
Luxol-fast blue. The central cerebral and cerebellar folia white matter exhibited pallor and
gliosis, while the corpus callosum and fornix stained normally with
Luxol-fast blue. Axons appeared intact on Bodian staining. Ultrastructural studies revealed fewer myelinated axons in affected puppies. Total
gangliosides in gray matter were elevated. Thin-layer chromatography demonstrated
GM1 ganglioside as the predominant
ganglioside. The amount of
cerebrosides and
sulfatides was reduced in the gray and white matter when compared to controls but the ratio in gray and white matter remained unchanged. Immunostaining of neutral
glycolipids disclosed increased amounts of
stage-specific embryonic antigen-1 glycolipid in gray matter. These findings suggest that canine models for
GM1 gangliosidosis are associated with abnormal myelin development which may be similar to the human disease.