Progressive thalamocortical neuron loss in Cln5 deficient mice: Distinct effects in Finnish variant late infantile NCL

Abstract

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.

Keywords

• Finnish variant late infantile neuronal ceroid lipofuscinosis
• Batten disease
• CLN5
• Thalamocortical neurodegeneration
• Lysosomal storage disorder