Biology Reference
In-Depth Information
Neurofilament light knockout mice develop normally, but the regener-
ation of myelinated axons following crush injury was found to be abnormal
with fewer newly regenerated myelinated axons in the sciatic nerve and
facial nerve (
Zhu, Couillard-Despres, & Julien, 1997
). BACE1 (
b
-site amy-
loid precursor protein cleaving enzyme 1) knockout and wild-type nerves
degenerated at a similar rate after axotomy. However, BACE1 knockout
mice had markedly enhanced clearance of axonal and myelin debris from
degenerated fibers, accelerated axonal regeneration, and earlier rein-
nervation of NMJs, compared with controls (
Farah et al., 2011
).
Fricker et al. (2011)
used a single-neuron labeling with inducible Cre-
mediated knockout animals, which enabled visualization of a subset of adult
myelinated sensory and motoneurons in which Nrg1 was inducibly mutated
by tamoxifen treatment. In uninjured mice, NRG1-deficient axons and the
associated myelin sheath were normal, and the NMJ demonstrated normal
apposition of presynaptic and postsynaptic components. After sciatic nerve
crush, NRG1 ablation resulted in severe defects in remyelination: axons
were either hypomyelinated or had no myelin sheath. NRG1-deficient
axons were also found to regenerate at a slower rate (
Fricker et al., 2011
).
Other studies use the overexpression of proteins in order to better
understand the role of a certain protein and to circumvent methodological
difficulties in drug delivery. For example, transgenic mice constitutively
expressing both interleukin 6 (IL-6) and its receptor (IL-6R) showed accel-
erated regeneration of the axotomized nerve (
Hirota, Kiyama, Kishimoto, &
Taga, 1996
). The overexpression of FGF-2 showed no difference in number
and size of myelinated fibers compared to wild-type mice in intact nerves.
On the other hand, 1 week after crush injury, the number of regenerated
axons was doubled and the myelin thickness was significantly smaller in
transgenic mice, but after 2 and 4 weeks, there were no differences in the
recovery of sensory and motor nerve fibers, showing that FGF-2 influences
early peripheral nerve regeneration by regulating Schwann cell proliferation,
axonal regrowth, and remyelination (
Jungnickel, Haase, Konitzer,
Timmer, & Grothe, 2006
). Transgenic mice expressing Nogo-C in periph-
eral Schwann cells regenerate axons less rapidly than do wild-type mice after
mid-thigh sciatic nerve crush (
Kim, Bonilla, Qiu, & Strittmatter, 2003
). On
the other hand, using regulated transgenic expression of Nogo-A in periph-
eral nerve Schwann cells,
Pot et al. (2002)
showed that axonal regeneration
and functional recovery are impaired after a sciatic nerve crush. Finally, the
overexpression of L1(adhesion molecule) in neurons had no effect on fem-
oral nerve function, numbers of quadriceps motoneurons, and myelinated
