Rescue of NGF-deficient mice I: transgenic expression of NGF in skin rescues mice lacking endogenous NGF.
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.
Harrison
Susan M W
SM
School of Biological Sciences, University of Kentucky, Lexington, KY 40506, USA.
Davis
Brian M
BM
Nishimura
Merry
M
Albers
Kathryn M
KM
Jones
Marc E
ME
Phillips
Heidi S
HS
D000818:Animals; D002470:Cell Survival / Q000235:genetics; D005260:Female; D005728:Ganglia, Sympathetic / Q000002:abnormalities / Q000166:cytology / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020932:Nerve Growth Factor / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism*; D009619:Nociceptors / Q000002:abnormalities / Q000166:cytology / Q000254:growth & development; D010146:Pain / Q000235:genetics / Q000378:metabolism; D017933:Peripheral Nervous System / Q000002:abnormalities* / Q000166:cytology / Q000254:growth & development; D011984:Sensory Receptor Cells / Q000002:abnormalities / Q000166:cytology / Q000254:growth & development; D012867:Skin / Q000254:growth & development* / Q000294:innervation / Q000378:metabolism; D012868:Skin Abnormalities / Q000235:genetics* / Q000378:metabolism; D017779:Sympathetic Fibers, Postganglionic / Q000002:abnormalities* / Q000166:cytology / Q000254:growth & development; D019076:Transgenes / Q000235:genetics; D012668:Trigeminal Ganglion / Q000002:abnormalities / Q000166:cytology / Q000254:growth & development
D020932:Nerve Growth Factor