Thalamocortical neuron loss and localized astrocytosis in the Cln3 Δex7/8 knock-in mouse model of Batten disease

Charlie C. Pontikis, Susan L. Cotman, Marcy E. MacDonald, Jonathan D. Cooper

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

Juvenile neuronal ceroid lipofuscinosis (JNCL) is the result of mutations in the Cln3 gene. The Cln3 knock-in mouse (Cln3Δex7/8) reproduces the most common Cln3 mutation and we have now characterized the CNS of these mice at 12 months of age. With the exception of the thalamus, Cln3 Δex7/8 homozygotes displayed no significant regional atrophy, but a range of changes in individual laminar thickness that resulted in variable cortical thinning across subfields. Stereological analysis revealed a pronounced loss of neurons within individual laminae of somatosensory cortex of affected mice and the novel finding of a loss of sensory relay thalamic neurons. These affected mice also exhibited profound astrocytic reactions that were most pronounced in the neocortex and thalamus, but diminished in other brain regions. These data provide the first direct evidence for neurodegenerative and reactive changes in the thalamocortical system in JNCL and emphasize the localized nature of these events.

Original languageEnglish
Pages (from-to)823-836
Number of pages14
JournalNeurobiology of Disease
Volume20
Issue number3
DOIs
StatePublished - Dec 2005

Keywords

  • Astrocytosis
  • Batten disease
  • CLN3
  • JNCL
  • Juvenile neuronal ceroid lipofuscinosis
  • Lysosomal storage disorder
  • Thalamocortical degeneration

Fingerprint

Dive into the research topics of 'Thalamocortical neuron loss and localized astrocytosis in the Cln3 Δex7/8 knock-in mouse model of Batten disease'. Together they form a unique fingerprint.

Cite this