Rescue of NGF-deficient mice I: transgenic expression of NGF in skin rescues mice lacking endogenous NGF
Rescue of NGF-deficient mice I: transgenic expression of NGF in skin rescues mice lacking endogenous NGF
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DOI：
10.1016/j.molbrainres.2003.12.004
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发表时间：
2004-03-30
期刊：
影响因子：
--
通讯作者：
Phillips, HS
中科院分区：
文献类型：
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作者：
Harrison, SMW;Davis, BM;Phillips, HS
缺乏功能性NGF基因的小鼠（ngf（-/-）小鼠）具有不到三分之一的正常感觉神经元，很少有交感节后神经元，并且在出生后不久死亡。我们在这里报告的K14角蛋白启动子控制下的神经生长因子的转基因表达可以拯救周围神经系统的一些元素，并恢复正常的生长和活力的神经生长因子（-/-）小鼠。而杂交转基因ngf（-/-）小鼠（ngfTKO）显示三叉神经节神经元的边缘拯救，CGRP阳性神经元的百分比恢复到正常。皮肤和脊髓中CGRP阳性终末的恢复也被发现，并伴随着对伤害性刺激的行为反应的恢复。ngfTKO小鼠显示正常数量的上级颈神经节神经元和皮肤交感神经支配的恢复。这些结果表明，通过将表达主要导向皮肤的转基因取代功能性NGF基因座可导致正常生长和活力。因此，最重要的功能，神经生长因子是不依赖于忠实重演的正常时空模式的基因表达。(C)2004 Elsevier B. V.保留所有权利。
Mice lacking a functional NGF gene (ngf(-/-) mice) have less than one third of the normal complement of sensory neurons, few sympathetic postganglionic neurons and die shortly after birth. We report here that transgenic expression of NGF under control of the K14 keratin promoter can rescue some elements of the peripheral nervous system and restore normal growth and viability to ngf(-/-) mice. While hybrid transgenic-ngf(-/-) mice (ngfTKOs) displayed marginal rescue of trigeminal ganglion neurons, the percentage of CGRP-positive neurons was restored to normal. Restoration of CGRP-positive terminals in skin and spinal cord was also found and accompanied by recovery of behavioral responses to noxious stimuli. ngfTKO mice displayed a normal number of superior cervical ganglion neurons and recovery of sympathetic innervation of skin. These results demonstrate that substitution of a functional NGF locus by a transgene directing expression largely to skin can result in normal growth and viability. Thus, the most vital functions of NGF are not dependent on faithful recapitulation of the normal spatiotemporal pattern of gene expression. (C) 2004 Elsevier B.V. All rights reserved.