Canavan Disease

Canavan disease (OMIM #271900) is a rare, autosomal-recessive neurodegenerative disorder within the leukodystrophy group, affecting the brain’s white matter. It leads to spongiform degeneration that impairs signal transmission in the brain. Symptoms usually appear between 3 to 6 months, including poor motor skills, feeding difficulties, abnormal muscle tone, and an unusually large head. Progression involves seizures, spasticity, swallowing issues, and muscle deterioration, causing severe developmental delays and neurological decline. More info

SHOW MOUSE MODELS

Pathogenic mechanism

Canavan disease is caused by mutations in the ASPA gene located on chromosome 17. This gene encodes the enzyme aspartoacylase, which plays a critical role in metabolizing N-acetylaspartic acid (NAA) – a molecule abundant in the brain, though its precise biological function remains not fully understood. Mutations in the ASPA gene result in reduced or absent aspartoacylase activity, leading to the accumulation of NAA in the brain. Excess NAA interferes with the formation and maintenance of the myelin sheath, a vital insulating layer that surrounds nerve fibers and enables the rapid and efficient transmission of nerve signals. Without proper myelin development, nerve signal conduction is impaired, leading to the progressive degeneration of white matter in the brain, manifesting as the characteristic symptoms of Canavan disease.

Available Mouse Models

in development