title: Regional and cellular neuropathology in the palmitoyl protein thioesterase-1 null mutant mouse model of infantile neuronal ceroid lipofuscinosis.
abstract: Infantile neuronal ceroid lipofuscinosis (INCL) is one of a group of fatal hereditary lysosomal storage disorders. Palmitoyl protein thioesterase 1 null mutant mice (PPT1-/-) now exist that accurately recapitulate many important disease features. The severely affected PPT1-/- mouse CNS exhibited reduced volume of both cortical and subcortical regions, but with sparing of the cerebellum. Pronounced differences existed in the extent of cortical thinning between different regions, due to lamina-specific effects upon neuronal survival. A dramatic reduction in cortical and hippocampal interneuron number was also evident, with different extents of specific interneuron loss depending upon the region and phenotypic marker. These neuronal changes were accompanied by widespread astrocytosis and localized microglial activation in restricted cortical and subcortical regions. This characterization of PPT1-/- mice not only provides defined pathological landmarks for understanding disease pathogenesis, but also provides an invaluable resource for subsequently judging the efficacy of therapeutic strategies.
authors.affiliation: Pediatric Storage Disorders Laboratory, and Department of Neuroscience, Institute of Psychiatry, King's College London, London SE5 8AF, UK.
authors.forename: Ellen
authors.initials: E
authors.lastname: Bible
authors.forename: Praveena
authors.initials: P
authors.lastname: Gupta
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Hofmann
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Cooper
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology; D001284:Atrophy; D004195:Disease Models, Animal; D005453:Fluorescence; D006624:Hippocampus / Q000473:pathology; D007395:Interneurons / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D017628:Microglia / Q000473:pathology; D019579:Neocortex / Q000473:pathology; D009472:Neuronal Ceroid-Lipofuscinoses / Q000473:pathology* / Q000503:physiopathology*; D017966:Pyramidal Cells / Q000473:pathology; D013869:Thiolester Hydrolases / Q000235:genetics*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005680:gamma-Aminobutyric Acid; D013869:Thiolester Hydrolases; C095299:palmitoyl-protein thioesterase