Altered expression of nerve growth factor in the skin of transgenic mice leads to changes in response to mechanical stimuli.
It has recently become clear that the neurotrophic factor, nerve growth factor, interacts specifically with nociceptive sensory neurons during development and maturity. Indeed, it may serve as a critical link between inflammation and the hyperalgesia that ensues in adult animals. Nerve growth factor is normally expressed in limiting amounts in target tissues of sensory and postganglionic sympathetic neurons. In the present study we have altered the basal level of nerve growth factor expression in the skin by producing transgenic mice that express a fusion gene construct containing either a sense or antisense nerve growth factor complementary DNA linked to the K14 keratin promoter. The K14-nerve growth factor transgene (sense or antisense) is abundantly expressed in skin from approximately embryonic day 15 and is then constitutively expressed throughout the life of the animal. In light of the fact that systemic administration of nerve growth factor to neonatal or adult rats leads to hyperalgesia, we have asked whether mice expressing the sense K14-nerve growth factor transgene exhibit similar sensory abnormalities and whether mice expressing the antisense nerve growth factor complementary DNA were hypoalgesic. Here we show that mice over-expressing nerve growth factor in skin display a profound hyperalgesia to noxious mechanical stimulation. Additionally, K14-nerve growth factor antisense mice displayed a profound hypoalgesia to the same stimuli.
Davis
B M
BM
Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington 40536.
Lewin
G R
GR
Mendell
L M
LM
Jones
M E
ME
Albers
K M
KM
D000818:Animals; D016373:DNA, Antisense / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation; D006930:Hyperalgesia / Q000209:etiology* / Q000235:genetics; D006987:Hypesthesia / Q000209:etiology / Q000235:genetics; D007633:Keratins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D009475:Neurons, Afferent / Q000502:physiology; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis*; D016037:Single-Blind Method; D012867:Skin / Q000378:metabolism*; D013314:Stress, Mechanical
D016373:DNA, Antisense; D018076:DNA, Complementary; D009414:Nerve Growth Factors; D011993:Recombinant Fusion Proteins; D007633:Keratins