Pontikis Charlie C, Cotman Susan L, MacDonald Marcy E, Cooper Jonathan D
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.
Neurobiol Dis. 2005 Dec;20(3):823-36. doi: 10.1016/j.nbd.2005.05.018. Epub 2005 Jul 11.
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.
青少年神经元蜡样脂褐质沉积症（JNCL）是由Cln3基因突变引起的。Cln3基因敲入小鼠（Cln3Deltaex7/8）重现了最常见的Cln3突变，并且我们现在已经对这些小鼠12个月大时的中枢神经系统进行了特征描述。除丘脑外，Cln3Deltaex7/8纯合子未表现出明显的区域萎缩，但各层厚度出现一系列变化，导致不同亚区的皮质变薄程度各异。体视学分析显示，受影响小鼠体感皮层各层内的神经元明显缺失，并且发现了感觉中继丘脑神经元缺失这一新现象。这些受影响的小鼠还表现出明显的星形细胞反应，在新皮层和丘脑中最为明显，但在其他脑区则有所减弱。这些数据为JNCL丘脑皮质系统中的神经退行性和反应性变化提供了首个直接证据，并强调了这些事件的局部性质。
