OVEREXPRESSION OF NGF WITHIN THE HEART OF TRANSGENIC MICE CAUSES HYPERINNERVATION, CARDIAC ENLARGEMENT, AND HYPERPLASIA OF ECTOPIC CELLS
OVEREXPRESSION OF NGF WITHIN THE HEART OF TRANSGENIC MICE CAUSES HYPERINNERVATION, CARDIAC ENLARGEMENT, AND HYPERPLASIA OF ECTOPIC CELLS
复制标题
DOI：
10.1006/dbio.1995.1146
复制
发表时间：
1995-05-01
影响因子：
2.7
通讯作者：
FEDEROFF, HJ
中科院分区：
文献类型：
--
作者：
HASSANKHANI, A;STEINHELPER, ME;FEDEROFF, HJ
神经生长因子（NGF）支持交感神经元和感觉神经元亚群的存活。在成人中，它参与维持反应神经元的神经递质表型。由给定靶组织合成的NGF的量决定其最终神经支配密度;那些未能接收足够的NGF的发育中的神经元经历凋亡。为了研究这一原则在特定靶器官中的影响，开发了转基因小鼠模型，其中通过将NGF小基因置于心脏特异性肌球蛋白重链启动子的转录控制下，在发育和成年心脏组织中增加NGF表达。转基因小鼠的心脏扩大继发于心肌质量的增加和大量异位细胞群的存在。免疫组化分析与神经标记物S-100显示染色的异位细胞的亚群，表明它们的衍生神经嵴。而神经元特异性蛋白质神经元特异性烯醇化酶的免疫染色显示心脏内异位细胞的另一个亚群的标记。心脏组织中的儿茶酚胺水平的测量结果显示，在转基因小鼠的显着升高，与交感神经支配过度。纵膈交感神经节的分析显示神经元的大小和数量都增加。在该模型中，增加的NGF表达产生心脏的神经支配过度，病理性心脏生长，以及异位神经嵴衍生细胞类型的募集和/或扩增。(C)出版社：Academic Press
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 cr-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. (C) 1995 Academic Press, Inc.