Canavan disease: studies on the knockout mouse.

@article{Matalon2006CanavanDS,
  title={Canavan disease: studies on the knockout mouse.},
  author={Reuben Matalon and Kimberlee Michals‐Matalon and Sankar Surendran and Stephen K. Tyring},
  journal={Advances in experimental medicine and biology},
  year={2006},
  volume={576},
  pages={
          77-93; discussion 361-3
        }
}
Canavan disease (CD) is an autosomal recessive disorder, characterized by spongy degeneration of the brain. Patients with CD have aspartoacylase (ASPA) deficiency, which results accumulation of N-acetylaspartic acid (NAA) in the brain and elevated excretion of urinary NAA. Clinically, patients with CD have macrocephaly, mental retardation and hypotonia. A knockout mouse for CD which was engineered, also has ASPA deficiency and elevated NAA. Molecular studies of the mouse brain showed abnormal… 
Chapter 62 – Canavan Disease
TLDR
Trials in knockout mice and Canavan patients are underway for potential treatment for Canavan disease, which is characterized by severe mental retardation, developmental delays, and early death.
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Canavan disease

References

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Knock‐out mouse for Canavan disease: a model for gene transfer to the central nervous system
TLDR
The successful creation of a knock‐out mouse for Canavan disease that can be used for gene transfer and the lack of an animal model has been a limiting factor in developing vectors for the treatment of CD.
Metabolic Changes in the Knockout Mouse for Canavan's Disease
TLDR
The creation of a knockout mouse for Canavan's disease is being used as a tool to investigate metabolic pathways in the mouse and correlate them with the patients with Canavan’s disease, where the level of glutamate is lower in the knockout mouse brain than in the wild-type mouse brain, similar to what has been found in children with Canvan's disease.
Two novel aspartoacylase gene (ASPA) missense mutations specific to Norwegian and Swedish patients with Canavan disease
TLDR
The aim has been to study the mutational spectrum of the aspartoacylase gene in Norwegian and Swedish patients of non-Jewish origin for patient management and for the design of rational molecular genetic diagnosis.
Mental retardation and hypotonia seen in the knock out mouse for Canavan disease is not due to succinate semialdehyde dehydrogenase deficiency
TLDR
The normal SSADH activity in theCD mouse brain suggests that mental retardation and hypotonia seen in the CD mouse is not due to SS ADH activity and if documented also in patients with CD.
Spongy degeneration of the brain, Canavan disease: biochemical and molecular findings.
TLDR
The carrier frequency for the two common mutations among Ashkenazi Jews was found to be surprisingly high, 1:37, which allowed for accurate diagnosis of Canavan disease, while prior to that, a brain biopsy was needed.
Molecular basis of Canavan disease.
  • R. Matalon, K. Michals‐Matalon
  • Medicine
    European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society
  • 1998
TLDR
Interestingly, only two mutations were found to be the basis for Canavan disease among 98% of individuals of Ashkenazi Jewish ancestry, while the molecular basis of Canavan Disease among non-Jewish individuals is caused by a wide range.
Aspartoacylase deficiency and Canavan disease in Saudi Arabia.
We found defective aspartoacylase activity in fibroblasts cultured from 12 patients with leukodystrophy clinically diagnosed as spongy degeneration of the brain (Canavan disease), three confirmed by
Cloning of the human aspartoacylase cDNA and a common missense mutation in Canavan disease
TLDR
The data suggest that the catalytic centre of aspartoacylase involves a triad of Ser, His and Glu residues, which has implications for diagnosis and screening of Canavan disease.
Adeno-associated virus-mediated aspartoacylase gene transfer to the brain of knockout mouse for canavan disease.
TLDR
Data indicate that rAAV-mediated ASPA delivery may be an interesting avenue for the treatment of CD and that in vivo NAA levels were reduced and pathology in sites unrelated to the injected areas showed no improvement in histopathology.
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