Aspartoacylase gene knockout results in severe vacuolation in the white matter and gray matter of the spinal cord in the mouse.
Canavan disease (CD) is a neurodegenerative disorder characterized by the spongy degeneration of the white matter of the brain. Aspartoacylase (ASPA) gene mutation resulting enzyme deficiency is the basic cause of CD. Whether the ASPA defect in CD affects the spinal cord has been investigated using the ASPA gene knockout mouse. Luxol fast blue-hematoxylin and eosin staining in the spinal cord of the knockout mouse showed vacuolation in both white matter and gray matter areas of cervical, thoracic, lumbar, and sacral segments of the spinal cord. However, more vacuoles were seen in the gray matter than the white matter of the spinal cord. ASPA activity in the cervical, thoracic, lumbar, and sacrococcygeal regions of the spinal cord was significantly lower in the knockout mouse compared to the wild type. The enzyme defect in the knockout mouse was also confirmed using the Western blot method. These observations suggest that the ASPA gene defect in the mouse leads to spinal cord pathology, and that these changes may be partly involved in the cause of the physiological/behavioral abnormalities seen in the knockout mouse, if documented also in patients with CD.
Surendran
Sankar
S
Department of Pediatrics, The University of Texas Medical Branch, Childrens Hospital, 301 University Boulevard, Galveston, TX 77555-0359, USA. ssurendr@utmb.edu
Campbell
Gerald A
GA
Tyring
Stephen K
SK
Matalon
Reuben
R
D000581:Amidohydrolases / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D017825:Canavan Disease / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D007794:Lameness, Animal / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009413:Nerve Fibers, Myelinated / Q000201:enzymology / Q000473:pathology; D009434:Neural Pathways / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D013116:Spinal Cord / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D013118:Spinal Cord Diseases / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D014617:Vacuoles / Q000473:pathology
D000581:Amidohydrolases; C019751:aspartoacylase