Le W, Conneely O M, He Y, Jankovic J, Appel S H
Department of Neurology, Baylor College of Medicine, Houston, Texas 77030, USA.
J Neurochem. 1999 Nov;73(5):2218-21.
Mutation in the Nurr1 gene, a member of the nuclear receptor superfamily, causes selective agenesis of dopaminergic neurons in the midbrain of null mice. Homozygous Nurr1 knockout mice (Nurr1-/-) die 1 day after birth, but heterozygous mice (Nurr1 +/-) survive postnatally without obvious locomotor deficits. Although adult Nurr1 +/- mice show significantly reduced Nurr1 protein levels in the substantia nigra (SN), they display a normal range of tyrosine hydroxylase-positive neuron numbers in the SN and normal levels of dopamine in the striatum. The reduction in Nurr1 expression in Nurr1 +/- mice, however, confers increased vulnerability to the selective dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) compared with wild-type (Nurr1 +/+) mice. This study suggests that Nurr1 may play an important role in maintaining mature mesencephalic dopaminergic neuron function and that a defect in Nurr1 may increase susceptibility to SN injury.
核受体超家族成员Nurr1基因的突变会导致纯合缺失小鼠中脑多巴胺能神经元选择性缺失。纯合Nurr1基因敲除小鼠（Nurr1-/-）出生后1天死亡，但杂合小鼠（Nurr1 +/-）出生后存活，且无明显运动缺陷。尽管成年Nurr1 +/-小鼠黑质（SN）中的Nurr1蛋白水平显著降低，但它们SN中酪氨酸羟化酶阳性神经元数量在正常范围内，纹状体中多巴胺水平也正常。然而，与野生型（Nurr1 +/+）小鼠相比，Nurr1 +/-小鼠中Nurr1表达的降低使其对选择性多巴胺能神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）的易感性增加。这项研究表明，Nurr1可能在维持成熟中脑多巴胺能神经元功能中起重要作用，且Nurr1缺陷可能会增加对黑质损伤的易感性。
