Thalamocortical neuron loss and localized astrocytosis in the Cln3Δex7/8 knock-in mouse model of Batten disease

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, Cln3Δex7/8 homozygote...

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Bibliographic Details
Published in:Neurobiology of disease 2005-12, Vol.20 (3), p.823-836
Main Authors: Pontikis, Charlie C., Cotman, Susan L., MacDonald, Marcy E., Cooper, Jonathan D.
Format: Article
Language:English
Subjects:
Astrocytosis
Batten disease
CLN3
JNCL
Juvenile neuronal ceroid lipofuscinosis
Lysosomal storage disorder
Thalamocortical degeneration
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Summary: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, Cln3Δex7/8 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.
ISSN:0969-9961
1095-953X
DOI:10.1016/j.nbd.2005.05.018