title: Thalamocortical neuron loss and localized astrocytosis in the Cln3Deltaex7/8 knock-in mouse model of Batten disease.
abstract: Juvenile neuronal ceroid lipofuscinosis (JNCL) is the result of mutations in the Cln3 gene. The Cln3 knock-in mouse (Cln3Deltaex7/8) 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, Cln3Deltaex7/8 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.
authors: Pediatric Storage Disorders Laboratory, Box P040, MRC Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, De Crespigny Park, King's College London, London SE5 8AF, UK.
authors: Charlie C
authors: CC
authors: Pontikis
authors: Susan L
authors: SL
authors: Cotman
authors: Marcy E
authors: ME
authors: MacDonald
authors: Jonathan D
authors: JD
authors: Cooper
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D016923:Cell Death / Q000235:genetics; D002566:Ceroid / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005911:Gliosis / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D002479:Inclusion Bodies / Q000235:genetics / Q000378:metabolism; D007395:Interneurons / Q000378:metabolism; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D018832:Molecular Chaperones / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009472:Neuronal Ceroid-Lipofuscinoses / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D013003:Somatosensory Cortex / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D013788:Thalamus / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology
chemical_list: D015415:Biomarkers; C102229:CLN3 protein, mouse; D002566:Ceroid; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones