Neuronal nitric oxide synthase alternatively spliced forms: Prominent functional localizations in the brain
Neuronal nitric oxide synthase alternatively spliced forms: Prominent functional localizations in the brain
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DOI：
10.1073/pnas.94.7.3396
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发表时间：
1997-04-01
影响因子：
11.1
通讯作者：
Snyder, SH
中科院分区：
文献类型：
--
作者：
Eliasson, MJL;Blackshaw, S;Snyder, SH
神经元一氧化氮合酶（nNOS）受到选择性剪接的影响，在外显子2 （nNOS(Delta/Delta)）靶向缺失的小鼠中，已经描述了两种选择性剪接形式，即缺乏外显子2的nNOS β和γ。我们通过原位杂交和免疫组织化学比较了野生型和nNOS（Delta/Delta）小鼠中天然nNOS α和nNOS β和γ的定位。通过免疫组织化学与NO形成化学计量。nNOS β在野生型动物的几个脑区中表现突出，在δ / δ型动物的皮层和纹状体中表现出2- 3倍的上调，大量的nNOS mRNA和蛋白的持续存在，以及耳蜗腹侧核和纹状体和外侧被膜核中明显的瓜氨酸免疫反应性（citr - ir），表明nNOS β是这些区域中酶的主要功能形式。以及可能其他未表征的剪接形式，似乎是离散脑区NO的重要生理来源，并可能解释nNOS（Delta/Delta）动物相对适度的损伤水平。
Neuronal nitric-oxide synthase (nNOS) is subject to alternative splicing, In mice with targeted deletions of exon 2 (nNOS(Delta/Delta)), two alternatively spliced forms, nNOS beta and gamma, which lack exon 2, have been described, We have compared localizations of native nNOS alpha and nNOS beta and gamma by in situ hybridization and immunohistochemistry in wild-type and nNOS(Delta/Delta) mice, To assess nNOS catalytic activity in intact animals we localized citrulline, which is formed stoichiometrically with NO, by immunohistochemistry. nNOS beta is prominent In several brain regions of wild-type animals and shows 2-to 3-fold up-regulation in the cortex and striatum of nNOS(Delta/Delta) animals, The persistence of much nNOS mRNA and protein, and distinct citrulline immunoreactivity (cit-IR) in the ventral cochlear nuclei and some cit-IR in the striatum and lateral tegmental nuclei, indicate that nNOS beta is a major functional form of the enzyme in these regions, Thus, nNOS beta, and possibly other uncharacterized splice forms, appear to be important physiological sources of NO in discrete brain regions and may account for the relatively modest level of impairment in nNOS(Delta/Delta) animals.