Progressive thalamocortical neuron loss in Cln5 deficient mice: Distinct effects in Finnish variant late infantile NCL.
Progressive thalamocortical neuron loss in Cln5 deficient mice: Distinct effects in Finnish variant late infantile NCL.
复制标题
Cln5 缺陷小鼠进行性丘脑皮质神经元丢失：对芬兰变异型婴儿晚期 NCL 的独特影响。
DOI：
10.1016/j.nbd.2009.02.001
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发表时间：
2009
影响因子：
6.1
通讯作者：
Cooper,JonathanD
中科院分区：
文献类型：
--
作者：
vonSchantz,Carina;Kielar,Catherine;Hansen,StineN;Pontikis,CharlieC;Alexander,NoreenA;Kopra,Outi;Jalanko,Anu;Cooper,JonathanD
芬兰变体LINCL（vLINCLFin）是CLN 5基因突变的结果。为了深入了解这种致命的儿科疾病的病理分期，我们对Cln 5缺陷小鼠（Cln 5 −/−）在疾病进展的不同阶段的CNS进行了体视学分析。与人类vLINCLFin一致，这些Cln 5 −/−小鼠表现出相对较晚发生的区域萎缩和普遍的皮质变薄和突触病理学，之前是丘脑皮质系统内的早期和局部胶质反应。然而，与其他形式的NCL形成鲜明对比的是，Cln 5 −/−小鼠的神经元损失始于皮质，随后仅发生在丘脑中继核内。然而，在其他NCL小鼠模型中，这种进行性丘脑皮质神经元损失仍然是最明显的视觉系统。这些数据为Cln 5 −/−小鼠丘脑皮质系统中神经元丢失的独特序列提供了意想不到的证据，与其他形式的NCL中所见完全相反。
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.