TY - JOUR
T1 - Progressive thalamocortical neuron loss in Cln5 deficient mice
T2 - Distinct effects in Finnish variant late infantile NCL
AU - von Schantz, Carina
AU - Kielar, Catherine
AU - Hansen, Stine N.
AU - Pontikis, Charlie C.
AU - Alexander, Noreen A.
AU - Kopra, Outi
AU - Jalanko, Anu
AU - Cooper, Jonathan D.
N1 - Funding Information:
These studies were supported by National Institutes of Health grant NS41930 (JDC) and European Commission 6th Framework Research Grant LSHM-CT-2003-503051 (JDC, AJ) and Academy of Finland, Centre of Excellence in Complex Disease Genetics Grant 213506 (AJ). The following non-profit agencies also contributed financially to this work: The Batten Disease Support and Research Association (JDC, CK), The Natalie Fund (JDC), The Batten Disease Family Association (JDC, CK) and the Remy Fund (JDC), The Sigrid Juselius Foundation (AJ), the Finnish Cultural Foundation (CVS) and the Helsinki Graduate School in Biotechnology and Molecular Biology (CVS). We would like to thank the other members of the PSDL and the Department of Molecular Medicine for their valuable contributions: Drs. Thomas Gillingwater, Andrew Wong and Alison Barnwell for their constructive comments on the manuscript.
PY - 2009/5
Y1 - 2009/5
N2 - Finnish variant LINCL (vLINCLFin) is the result of mutations in the CLN5 gene. To gain insights into the pathological staging of this fatal pediatric disorder, we have undertaken a stereological analysis of the CNS of Cln5 deficient mice (Cln5-/-) at different stages of disease progression. Consistent with human vLINCLFin, these Cln5-/- mice displayed a relatively late onset regional atrophy and generalized cortical thinning and synaptic pathology, preceded by early and localized glial responses within the thalamocortical system. However, in marked contrast to other forms of NCL, neuron loss in Cln5-/- mice began in the cortex and only subsequently occurred within thalamic relay nuclei. Nevertheless, as in other NCL mouse models, this progressive thalamocortical neuron loss was still most pronounced within the visual system. These data provide unexpected evidence for a distinctive sequence of neuron loss in the thalamocortical system of Cln5-/- mice, diametrically opposed to that seen in other forms of NCL.
AB - Finnish variant LINCL (vLINCLFin) is the result of mutations in the CLN5 gene. To gain insights into the pathological staging of this fatal pediatric disorder, we have undertaken a stereological analysis of the CNS of Cln5 deficient mice (Cln5-/-) at different stages of disease progression. Consistent with human vLINCLFin, these Cln5-/- mice displayed a relatively late onset regional atrophy and generalized cortical thinning and synaptic pathology, preceded by early and localized glial responses within the thalamocortical system. However, in marked contrast to other forms of NCL, neuron loss in Cln5-/- mice began in the cortex and only subsequently occurred within thalamic relay nuclei. Nevertheless, as in other NCL mouse models, this progressive thalamocortical neuron loss was still most pronounced within the visual system. These data provide unexpected evidence for a distinctive sequence of neuron loss in the thalamocortical system of Cln5-/- mice, diametrically opposed to that seen in other forms of NCL.
KW - Batten disease
KW - CLN5
KW - Finnish variant late infantile neuronal ceroid lipofuscinosis
KW - Lysosomal storage disorder
KW - Thalamocortical neurodegeneration
UR - http://www.scopus.com/inward/record.url?scp=64649097377&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2009.02.001
DO - 10.1016/j.nbd.2009.02.001
M3 - Article
C2 - 19385065
AN - SCOPUS:64649097377
VL - 34
SP - 308
EP - 319
JO - Neurobiology of Disease
JF - Neurobiology of Disease
SN - 0969-9961
IS - 2
ER -