Regional and cellular neuropathology in the palmitoyl protein thioesterase-1 null mutant mouse model of infantile neuronal ceroid lipofuscinosis

Ellen Bible, Praveena Gupta, Sandra L. Hofmann, Jonathan D. Cooper

Research output: Contribution to journalArticle

116 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)346-359
Number of pages14
JournalNeurobiology of Disease
Volume16
Issue number2
DOIs
StatePublished - Jul 2004
Externally publishedYes

Fingerprint

Neuronal Ceroid-Lipofuscinoses
Interneurons
Gliosis
Cerebellum
palmitoyl-protein thioesterase
Neuropathology
Ceroid lipofuscinosis, neuronal 1, infantile
Therapeutics

Keywords

  • CLN1
  • GABAergic interneurons
  • Glial activation
  • INCL
  • Lysosomal storage disorder
  • Neuronal ceroid lipofuscinosis
  • PPT1

ASJC Scopus subject areas

  • Neurology

Cite this

Regional and cellular neuropathology in the palmitoyl protein thioesterase-1 null mutant mouse model of infantile neuronal ceroid lipofuscinosis. / Bible, Ellen; Gupta, Praveena; Hofmann, Sandra L.; Cooper, Jonathan D.

In: Neurobiology of Disease, Vol. 16, No. 2, 07.2004, p. 346-359.

Research output: Contribution to journalArticle

@article{d2fd3a83547346e5ab6128d9fb1a08e7,
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.",
keywords = "CLN1, GABAergic interneurons, Glial activation, INCL, Lysosomal storage disorder, Neuronal ceroid lipofuscinosis, PPT1",
author = "Ellen Bible and Praveena Gupta and Hofmann, {Sandra L.} and Cooper, {Jonathan D.}",
year = "2004",
month = "7",
doi = "10.1016/j.nbd.2004.02.010",
language = "English (US)",
volume = "16",
pages = "346--359",
journal = "Neurobiology of Disease",
issn = "0969-9961",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Regional and cellular neuropathology in the palmitoyl protein thioesterase-1 null mutant mouse model of infantile neuronal ceroid lipofuscinosis

AU - Bible, Ellen

AU - Gupta, Praveena

AU - Hofmann, Sandra L.

AU - Cooper, Jonathan D.

PY - 2004/7

Y1 - 2004/7

N2 - 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.

AB - 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.

KW - CLN1

KW - GABAergic interneurons

KW - Glial activation

KW - INCL

KW - Lysosomal storage disorder

KW - Neuronal ceroid lipofuscinosis

KW - PPT1

UR - http://www.scopus.com/inward/record.url?scp=2942597781&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2942597781&partnerID=8YFLogxK

U2 - 10.1016/j.nbd.2004.02.010

DO - 10.1016/j.nbd.2004.02.010

M3 - Article

VL - 16

SP - 346

EP - 359

JO - Neurobiology of Disease

JF - Neurobiology of Disease

SN - 0969-9961

IS - 2

ER -