Canavan disease: studies on the knockout mouse.

  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},
          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… 

N-Acetylaspartate Synthase Deficiency Corrects the Myelin Phenotype in a Canavan Disease Mouse Model But Does Not Affect Survival Time

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.

rAAV Gene Therapy in a Canavan's Disease Mouse Model Reveals Immune Impairments and an Extended Pathology Beyond the Central Nervous System.

It is demonstrated for the first time that AspA deficiency, possibly through excessive N-acetyl aspartic acid accumulation, elicits both a peripheral and CNS immune response in CD mice, and established a role for peripheral tissues in CD pathology.

Progressive Brain Disorders in Childhood

This book is essential for teaching medical practitioners how to promptly identify neurological regression during childhood development and investigate disorders in sufficient depth to be able to arrive at a precise syndromic diagnosis, plan appropriate management for the patient, and offer advice to caregivers.

D-Aspartate treatment stimulates differentiation of oligodendrocyte precursors, prevents demyelination and accelerates remyelination in the cuprizone mouse model of Multiple Sclerosis

The in vitro results suggest that D-Asp stimulates oligodendrocyte development through a mechanism involving calcium signaling through the glutamate receptors AMPA and NMDA and the Na+/Ca23+ exchanger NCX3 plays an important role during oligodendedrocytes differentiation and myelin formation.

Regulation and roles of neuronal diacylglycerol kinases: a lipid perspective

In this review, what is currently understood about the localization and regulation of the neuronal DGKs in the mammalian CNS is summarized.

Canavan disease

Role of PDGF-A-Activated ERK Signaling Mediated FAK-Paxillin Interaction in Oligodendrocyte Progenitor Cell Migration

PDGF-A induces OPC migration in an ERK-dependent mechanism via regulation of actin reorganization and FAK-Paxillin interaction and interaction of focal adhesion kinase, Paxillin, and pERK signals are impaired in OPCs treated with the MEK inhibitor U0126.



Knock‐out mouse for Canavan disease: a model for gene transfer to the central nervous system

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

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.

Spongy degeneration of the brain, Canavan disease: biochemical and molecular findings.

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. MatalonK. Michals‐Matalon
  • Medicine
    European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society
  • 1998

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

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.

Prevalence of Canavan disease heterozygotes in the New York metropolitan Ashkenazi Jewish population.

The frequency of the E285A and Y231X mutations, which results in the conversion from a tyrosine codon to terminator codon at position 231, provide a detection rate >97% in this population of Ashkenazi Jewish patients, is determined from a panel of unaffected individuals who live in the New York metropolitan area.