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… 
Chapter 62 – Canavan Disease
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
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
Emerging evidence support a role for some D-Aminoacids as neurotrasmitters and neuromodulators, since they are found in mammalian tissues and also in the central nervous system (CNS) (Hashimoto and
Myelin and Myelination
Myelin and myelination are described in this section, with emphasis on points relevant to neurotoxic mechanisms of chemicals that target myelin.
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.
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.
Canavan disease


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.
Two novel aspartoacylase gene (ASPA) missense mutations specific to Norwegian and Swedish patients with Canavan disease
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
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.
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
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
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.
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.