Baffi J S, Palkovits M, Castillo S O, Mezey E, Nikodem V M
National Institutes of Health, Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA.
Neuroscience. 1999;93(2):631-42. doi: 10.1016/s0306-4522(99)00124-4.
The orphan nuclear receptor Nurr1 is a transcription factor that belongs to the steroid/thyroid hormone receptor superfamily and is expressed in many regions of the brain. To determine the physiological role of Nurr1, we previously generated mice with a null mutation in the Nurr1 gene. Nurr1-null mice appear to develop normally but die within 12 h after birth. Subsequent analysis revealed the absence of neurotransmitter dopamine and tyrosine hydroxylase immunoreactivity in the central dopaminergic area of newborn pups. Herein, using in situ hybridization histochemistry, we show that Nurr1 is expressed only in subset of catecholamine producing neurons (A2 partly, A8-A10 and A11 catecholaminergic cell groups), and is excluded from the norepinephrine producing neurons (A1, A2, A5-A6 catecholaminergic cell groups). Nurr1 was not expressed in the dopamine synthesizing cell groups (A12-A16 catecholaminergic cell groups) of the diencephalon and the olfactory bulb. As previously shown and confirmed in this study, tyrosine hydroxylase immunoreactivity was absent in the substantia nigra and ventral tegmental area of Nurr1-deficient mice. However, the loss of Nurr1 expression in A2 and A11 dopaminergic neurons did not affect their tyrosine hydroxylase immunoreactivity. This study begins to dissect cues necessary for understanding the complex regulation of the catecholaminergic biosynthetic pathway with regard to local, chemical and developmental changes in the brain.
孤儿核受体Nurr1是一种转录因子，属于类固醇/甲状腺激素受体超家族，在大脑的许多区域均有表达。为了确定Nurr1的生理作用，我们先前培育出了Nurr1基因发生无效突变的小鼠。Nurr1基因敲除小鼠似乎发育正常，但在出生后12小时内死亡。随后的分析显示，新生幼崽中枢多巴胺能区域缺乏神经递质多巴胺和酪氨酸羟化酶免疫反应性。在此，我们采用原位杂交组织化学方法显示，Nurr1仅在一部分儿茶酚胺生成神经元（部分A2、A8 - A10和A11儿茶酚胺能细胞群）中表达，而在去甲肾上腺素生成神经元（A1、A2、A5 - A6儿茶酚胺能细胞群）中不表达。Nurr1在间脑和嗅球的多巴胺合成细胞群（A12 - A16儿茶酚胺能细胞群）中不表达。正如先前所示并在本研究中得到证实，Nurr1基因缺陷小鼠的黑质和腹侧被盖区缺乏酪氨酸羟化酶免疫反应性。然而，A2和A11多巴胺能神经元中Nurr1表达的缺失并不影响其酪氨酸羟化酶免疫反应性。本研究开始剖析理解儿茶酚胺能生物合成途径在大脑局部、化学和发育变化方面复杂调控所必需的线索。
