RGD Reference Report - Effects of AAV-2-mediated aspartoacylase gene transfer in the tremor rat model of Canavan disease. - Rat Genome Database

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Effects of AAV-2-mediated aspartoacylase gene transfer in the tremor rat model of Canavan disease.

Authors: McPhee, SW  Francis, J  Janson, CG  Serikawa, T  Hyland, K  Ong, EO  Raghavan, SS  Freese, A  Leone, P 
Citation: McPhee SW, etal., Brain Res Mol Brain Res. 2005 Apr 27;135(1-2):112-21.
RGD ID: 1599298
Pubmed: (View Article at PubMed) PMID:15857674
DOI: Full-text: DOI:10.1016/j.molbrainres.2004.12.007

The tremor rat is a spontaneous epilepsy model with a seizure phenotype caused by a deletion in the aspartoacylase (ASPA) gene. The absence of ASPA expression in these animals results in undetectable levels of enzyme activity and the accumulation of the substrate N-acetyl-aspartate (NAA) in brain, leading to generalized myelin vacuolation and severe motor and cognitive impairment. In support of human gene therapy for CD, recombinant adeno-associated viral vector (AAV-2) expressing ASPA was stereotactically delivered to the tremor rat brain and effects on the mutant phenotype were measured. AAV-ASPA gene transfer resulted in elevated aspartoacylase bioactivity compared to untreated mutant animals and elicited a significant decrease in the pathologically elevated whole-brain NAA levels. Assessment of motor function via quantitative rotorod testing demonstrated that rats injected with AAV-ASPA significantly improved on tests of balance and coordinated locomotion compared to animals receiving control vectors. This study provides evidence that AAV-2-mediated aspartoacylase gene transfer to the brain improves biochemical and behavioral deficits in tremor rat mutants (tm/tm) and supports the rationale of human gene transfer for Canavan disease.


Disease Annotations    
Canavan disease  (IAGP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Aspa  (aspartoacylase)

Genes (Mus musculus)
Aspa  (aspartoacylase)

Genes (Homo sapiens)
ASPA  (aspartoacylase)

Additional Information