Loss of locus coeruleus neurons and reduced startle in parkin null mice
Loss of locus coeruleus neurons and reduced startle in parkin null mice
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DOI：
10.1073/pnas.0401297101
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发表时间：
2004-07-20
影响因子：
11.1
通讯作者：
Dawson, TM
中科院分区：
文献类型：
--
作者：
von Coelln, R;Thomas, B;Dawson, TM
帕金森病（PD）是最常见的神经退行性运动障碍，其病理特征是黑质腹侧部和蓝斑等区域的儿茶酚胺能神经元变性。常染色体隐性遗传型青少年帕金森综合征（ARJP）是由编码parkin的PARK 2基因突变引起的，是PD最常见的家族性形式。大多数ARJP相关的parkin突变被认为是功能缺失突变;然而，ARJP的发病机制仍然知之甚少。在这里，我们报告的帕金基因敲除小鼠帕金基因外显子7的目标删除的一代。这些小鼠显示蓝斑中的儿茶酚胺能神经元的损失和伴随的中枢神经系统的离散区域中的去甲肾上腺素的损失。此外，去甲肾上腺素依赖性惊吓反应显著减少。黑质纹状体多巴胺能系统未显示任何损害。这种小鼠模型将有助于更好地了解parkin功能和parkin相关PD的机制。
Parkinson's disease (PD) is the most common neurodegenerative movement disorder and is characterized pathologically by degeneration of catecholaminergic neurons of the substantia nigra pars compacta and locus coeruleus, among other regions. Autosomal-recessive juvenile Parkinsonism (ARJP) is caused by mutations in the PARK2 gene coding for parkin and constitutes the most common familial form of PD. The majority of ARJP-associated parkin mutations are thought to be loss of function-mutations; however, the pathogenesis of ARJP remains poorly understood. Here, we report the generation of parkin null mice by targeted deletion of parkin exon 7. These mice show a loss of catecholaminergic neurons in the locus coeruleus and an accompanying loss of norepinephrine in discrete regions of the central nervous system. Moreover, there is a dramatic reduction of the norepinephrine-dependent startle response. The nigrostriatal dopaminergic system does not show any impairment. This mouse model will help gain a better understanding of parkin function and the mechanisms underlying parkin-associated PD.