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… 
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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.
N-Acetylaspartate Synthase Deficiency Corrects the Myelin Phenotype in a Canavan Disease Mouse Model But Does Not Affect Survival Time
TLDR
It is demonstrated that acetate derived from NAA is not essential for myelin lipid synthesis and that loss of NAA-derived acetate does not cause the myelin phenotype of Aspanur7/nur7 mice, which supports the hypothesis that NAA accumulation is the major factor in the development of CD.
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TLDR
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References

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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.
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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.
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TLDR
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TLDR
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TLDR
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  • Medicine
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TLDR
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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.
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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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