Document Detail


Abnormalities in neural progenitor cells in a dog model of lysosomal storage disease.
MedLine Citation:
PMID:  17882020     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Lysosomal storage disorders constitute a large group of genetic diseases, many of which are characterized by mental retardation and other neurologic symptoms. The mechanisms of neural dysfunction remain poorly understood. Because neural progenitor cells (NPCs) are fundamentally important to normal brain development and function, we investigated NPC properties in a canine model of mucopolysaccharidosis VII (MPS VII). MPS VII is a lysosomal storage disorder characterized by defects in the catabolism of glycosaminoglycans. NPCs were isolated from the olfactory bulb, cerebellum, and striatal subventricular zone of normal and MPS VII (beta-glucuronidase-deficient) postnatal dog brains. Canine NPCs (cNPCs) from normal and MPS VII brains had similar growth curves, but cerebellar-derived cNPCs grew significantly slower than those derived from other regions. In differentiation assays, MPS VII cNPCs from the striatal subventricular zone and cerebellum generated fewer mature neuronal and/or glial cells than normal, and MPS VII olfactory bulb-derived cNPCs retained significantly more phenotypically immature cells. These differences were only present at the earliest time point after isolation; at later passages, there were no differences attributable to genotype. The data suggest that MPS VII cNPCs respond differently to developmental cues in vivo, probably because of the diseased neural microenvironment rather than intrinsic cellular deficits.
Authors:
Raquel M Walton; John H Wolfe
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of neuropathology and experimental neurology     Volume:  66     ISSN:  0022-3069     ISO Abbreviation:  J. Neuropathol. Exp. Neurol.     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-09-20     Completed Date:  2007-10-26     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  2985192R     Medline TA:  J Neuropathol Exp Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  760-9     Citation Subset:  IM    
Affiliation:
W F Goodman Center for Comparative Medical Genetics, and Department of Pathology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Cell Differentiation / genetics
Cells, Cultured
Cerebellum / pathology
Cerebral Ventricles / growth & development,  pathology*
Disease Models, Animal
Dogs
Lysosomal Storage Diseases / genetics,  pathology*
Mucopolysaccharidosis VII / genetics*
Neurons / pathology*
Stem Cells / pathology*
Grant Support
ID/Acronym/Agency:
DK42707/DK/NIDDK NIH HHS; DK46637/DK/NIDDK NIH HHS; DK63973/DK/NIDDK NIH HHS; RR02512/RR/NCRR NIH HHS; RR07063/RR/NCRR NIH HHS

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Telepathology for intraoperative neuropathologic consultations at an academic medical center: a 5-ye...
Next Document:  Iodixanol: risk of subsequent contrast nephropathy in cancer patients with underlying renal insuffic...