Canavan disease: studies on the knockout mouse.
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 expression of multiple genes in addition to ASPA deficiency. Adenoassociated virus mediated gene transfer and stem cell therapy in the knockout mouse are the latest attempts to alter pathophysiology in the CD mouse.
Matalon
Reuben
R
Department of Pediatrics, University of Texas Medical Branch, Galveston, TX 77555, USA. rmatalon@utmb.edu
Michals-Matalon
Kimberlee
K
Surendran
Sankar
S
Tyring
Stephen K
SK
D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017825:Canavan Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D004151:Dipeptides / Q000378:metabolism; D018390:Gene Targeting; D015316:Genetic Therapy; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D033581:Stem Cell Transplantation; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D004151:Dipeptides; C027172:isospaglumic acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000581:Amidohydrolases; C019751:aspartoacylase