Transgenic mice expressing nerve growth factor in smooth muscle cells

Abstract

Ectopic expression of nerve growth factor (NGF) in transgenic mice leads to site-specific sympathetic sprouting. Smooth muscle cells in the intestines, urinary bladder, and arteries have been shown to express NGF. To address whether enhanced NGF production among these different organ systems stimulates comparable patterns of sympathetic collateral growth, we generated transgenic mice that express NGF under the control of the smooth muscle alpha-actin promoter. In response to elevated levels of NGF protein in the colon, bladder, and arteries/arterioles, sympathetic axons displayed robust sprouting only in the colon and bladder. These data reveal that, unlike most other peripheral tissues, sympathetic efferents in adult mammalian arteries/arterioles do not undergo collateral growth in response to increased levels of smooth muscle-derived NGF.

Overexpression of NGF in mouse urothelium leads to neuronal hyperinnervation, pelvic sensitivity, and changes in urinary bladder function

“…This is consistent with the idea that NGF functions as a target-derived trophic factor capable of stimulating or modulating neuronal development, growth, and survival (41). It is also consistent with the findings from several different tissue-specific NGF transgenic mouse lines, in which NGF overexpression in pancreatic islets, pulmonary airways, skin, heart, brain, and smooth muscle resulted in the common phenotypic finding of increased sprouting by sympathetic efferent and sensory afferent nerve fibers to target organs and in many cases associated ganglion (2,20,27,28,36,37,39,45,46,104).…”

Myenteric expression of nerve growth factor and the p75 neurotrophin receptor regulate axonal remodeling as a consequence of colonic inflammation in mice

“…Ectopic expression of NGF in transgenic mice does, in fact, trigger increased neuronal numbers, somal hypertrophy, and/or increased axonal densities by trkA + sensory and sympathetic neurons (Albers et al, 1994, Elliott et al, 2009, Edwards et al, 1989. Examination of these biological features among NOS1 + myenteric neurons revealed no enhanced survival, somal swelling, or axonal sprouting in response to high levels of NGF protein in the colons of adult SMPpr-NGF transgenic mice, as compared to age-matched wild type siblings.…”

“…Adult SMPpr-NGF transgenic mice, which express NGF under the control of the -actin smooth muscle (SMP) promoter), display increased levels of NGF protein in the distal colon (Elliott et al 2009). Comparisons of NOS1 + axonal densities in adult NGF/p75 +/+ , NGF/p75 -/-, p75 +/+ , and p75 -/-siblings revealed no significant differences among the four genotypes ( Fig.…”

Novel Multi-System Functional Gains via Task Specific Training in Spinal Cord Injured Male Rats

“…48,50-52 These plasticity phenomena have been linked to increased production of NGF in bladder tissues. 49,[53][54][55][56] Given that step training affected bladder function and that training affects neurotrophin production in other tissues (muscle, spinal cord), 57,58 we assessed neurotrophin mRNA in the bladders of both trained and non-trained rats by qPCR. The expression level of each transcript was determined relative to b-actin.…”