Regional and cellular neuropathology in the palmitoyl protein thioesterase-1 null mutant mouse model of infantile neuronal ceroid lipofuscinosis
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 red...
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| Format: | Article |
| Language: | English |
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Elsevier
2004-07-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996104000440 |
| _version_ | 1819163440622600192 |
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| author | Ellen Bible Praveena Gupta Sandra L Hofmann Jonathan D Cooper |
| author_facet | Ellen Bible Praveena Gupta Sandra L Hofmann Jonathan D Cooper |
| author_sort | Ellen Bible |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T17:44:10Z |
| format | Article |
| id | doaj.art-14c7f92442c848c3aaee91466866f84b |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-22T17:44:10Z |
| publishDate | 2004-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-14c7f92442c848c3aaee91466866f84b2022-12-21T18:18:20ZengElsevierNeurobiology of Disease1095-953X2004-07-01162346359Regional and cellular neuropathology in the palmitoyl protein thioesterase-1 null mutant mouse model of infantile neuronal ceroid lipofuscinosisEllen Bible0Praveena Gupta1Sandra L Hofmann2Jonathan D Cooper3Pediatric Storage Disorders Laboratory, Institute of Psychiatry, King's College London, London SE5 8AF, UK; Department of Neuroscience, Institute of Psychiatry, King's College London, London SE5 8AF, UK; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-8593, USAPediatric Storage Disorders Laboratory, Institute of Psychiatry, King's College London, London SE5 8AF, UK; Department of Neuroscience, Institute of Psychiatry, King's College London, London SE5 8AF, UK; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-8593, USAPediatric Storage Disorders Laboratory, Institute of Psychiatry, King's College London, London SE5 8AF, UK; Department of Neuroscience, Institute of Psychiatry, King's College London, London SE5 8AF, UK; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-8593, USAPediatric Storage Disorders Laboratory, Institute of Psychiatry, King's College London, London SE5 8AF, UK; Department of Neuroscience, Institute of Psychiatry, King's College London, London SE5 8AF, UK; Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-8593, USAInfantile 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.http://www.sciencedirect.com/science/article/pii/S0969996104000440Neuronal ceroid lipofuscinosisCLN1PPT1INCLGABAergic interneuronsGlial activation |
| spellingShingle | Ellen Bible Praveena Gupta Sandra L Hofmann Jonathan D Cooper Regional and cellular neuropathology in the palmitoyl protein thioesterase-1 null mutant mouse model of infantile neuronal ceroid lipofuscinosis Neurobiology of Disease Neuronal ceroid lipofuscinosis CLN1 PPT1 INCL GABAergic interneurons Glial activation |
| title | Regional and cellular neuropathology in the palmitoyl protein thioesterase-1 null mutant mouse model of infantile neuronal ceroid lipofuscinosis |
| title_full | Regional and cellular neuropathology in the palmitoyl protein thioesterase-1 null mutant mouse model of infantile neuronal ceroid lipofuscinosis |
| title_fullStr | Regional and cellular neuropathology in the palmitoyl protein thioesterase-1 null mutant mouse model of infantile neuronal ceroid lipofuscinosis |
| title_full_unstemmed | Regional and cellular neuropathology in the palmitoyl protein thioesterase-1 null mutant mouse model of infantile neuronal ceroid lipofuscinosis |
| title_short | Regional and cellular neuropathology in the palmitoyl protein thioesterase-1 null mutant mouse model of infantile neuronal ceroid lipofuscinosis |
| title_sort | regional and cellular neuropathology in the palmitoyl protein thioesterase 1 null mutant mouse model of infantile neuronal ceroid lipofuscinosis |
| topic | Neuronal ceroid lipofuscinosis CLN1 PPT1 INCL GABAergic interneurons Glial activation |
| url | http://www.sciencedirect.com/science/article/pii/S0969996104000440 |
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