Hassankhani A, Steinhelper M E, Soonpaa M H, Katz E B, Taylor D A, Andrade-Rozental A, Factor S M, Steinberg J J, Field L J, Federoff H J
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Dev Biol. 1995 May;169(1):309-21. doi: 10.1006/dbio.1995.1146.
Nerve growth factor (NGF) supports the survival of developing sympathetic and a subpopulation of sensory neurons. In the adult it participates in maintenance of the neurotransmitter phenotype of responsive neurons. The amount of NGF synthesized by a given target tissue determines its final innervation density; those developing neurons that fail to receive sufficient NGF undergo apoptosis. In order to examine the ramifications of this principle in the context of a specific target organ, a transgenic mouse model was developed in which NGF expression was increased in developing and adult cardiac tissue by placing a NGF minigene under the transcriptional control of the cardiac-specific alpha-myosin heavy chain promoter. Transgenic mice developed cardiac enlargement secondary to both an increase in myocardial mass and the presence of an abundant ectopic cell population. Immunohistochemical analyses with the neural marker S-100 revealed staining of a subpopulation of ectopic cells, suggesting their derivation from the neural crest. Whereas immunostaining for the neuronal-specific protein neuron-specific enolase demonstrated labeling of another subpopulation of ectopic cells within the heart. Measurements of cardiac tissue catecholamine levels revealed a marked elevation in transgenic mice, consistent with sympathetic hyperinnervation. Analysis of mediastinal sympathetic ganglia revealed increases in both the size and the number of neurons. In this model, increased expression of NGF produced hyperinnervation of the heart, pathological cardiac growth, and the recruitment and/or expansion of an ectopic, neural crest-derived cell type.
神经生长因子（NGF）支持发育中的交感神经元和一部分感觉神经元的存活。在成体中，它参与维持反应性神经元的神经递质表型。特定靶组织合成的NGF量决定了其最终的神经支配密度；那些未能获得足够NGF的发育中神经元会发生凋亡。为了在特定靶器官的背景下研究这一原理的影响，构建了一种转基因小鼠模型，通过将NGF小基因置于心脏特异性α-肌球蛋白重链启动子的转录控制下，使发育中和成年心脏组织中的NGF表达增加。转基因小鼠出现心脏扩大，这继发于心肌质量增加和大量异位细胞群的存在。用神经标志物S-100进行的免疫组织化学分析显示异位细胞亚群有染色，提示它们源自神经嵴。而针对神经元特异性蛋白神经元特异性烯醇化酶的免疫染色显示心脏内另一个异位细胞亚群有标记。心脏组织儿茶酚胺水平的测量显示转基因小鼠显著升高，这与交感神经超支配一致。对纵隔交感神经节的分析显示神经元的大小和数量均增加。在这个模型中，NGF表达增加导致心脏超支配、病理性心脏生长以及一种异位的、源自神经嵴的细胞类型的募集和/或扩增。
