Analysis Tools
behavior/neurological
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• at P60, mice require significantly more time to cross the horizontal bar in a beam balance test, exhibit a reduced duration on the coat hanger after being placed in the middle of the lower horizontal bar, and show a significant decrease in rotarod residence/stay time before falling in the rotarod test
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• at P60, mice show a significant reduction in forelimb grip strength
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• 2.6% of mice exhibit abnormal posture at P20
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• mice exhibit abnormal posture of the forelimbs and hindlimbs
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• at P20, mice appear to walk with a staggered gait and abnormal posture
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• at P60, the latency to the onset of hindpaw licking or shaking is significantly increased at 48-, 50- and 52 degrees Celsius in the hot plate test, indicating nociceptive hyposensitivity
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• at P60, mice exhibit a significant reduction in treadmill lane distance in a treadmill assay
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limbs/digits/tail
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• at P20, severe paw injuries and deformities are observed in both forelimbs and hindlimbs
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• 31.1% of mice display abnormal hindlimb deficiency and swelling
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nervous system
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• at P3, radial sorting of axons by Schwann cells (SCs) is delayed in the sciatic nerve
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• at P7, a few axons are ensheathed by promyelinating Schwann cells (SCs) and abnormal multilayered myelin sheath structures are formed but not tightly attached to axons in the sciatic nerve; abnormal folding is also observed
• at P14, misfolded myelin, focal hypermyelination, myelin debris, tomacula, and invaginating recurrent loops are noted in the sciatic nerve; the percentage of sciatic nerve axonal myelin abnormalities is significantly elevated
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• at P7, myelin labeled by MBP staining is significantly reduced in the sciatic nerve
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• at P21, mice show impaired survival of some subtypes of dorsal root ganglion (DRG) sensory neurons, as shown by a slight reduction in the number of proprioceptive neurons (TrkC+, Runx3+, PV+) and Ret+ neurons in the DRG
• however, the number of most DRG neuron subtypes is unchanged at E16.5, suggesting that early neuronal fate specification is largely normal
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• at P21, mice show a slight reduction of the number of proprioceptive neurons (TrkC+, Runx3+, PV+) neurons in the DRG
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• TEM analysis shows features of axonal degeneration in the sciatic nerve, including axon shrinkage or axonal loss (empty myelin sheath), accumulation of mitochondria and lysosomes in the axoplasm, and splitting or contortion of the remaining myelin sheath
• at P7, expression of acetylated alpha-tubulin (a marker of stable microtubules) is specifically decreased in the sciatic nerve, with no apparent change in alpha-tubulin and acetylated alpha-tubulin levels found in spinal cord or brain tissues
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• percentage of myelinated axons in the sciatic nerve is significantly reduced at P3 and P7 but normal at P14, with no significant change in total axon number seen at P3, P7 or P14
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• at P21, TEM analysis of myelinated fibers in the sciatic nerve shows dysmyelination, including comma-shaped outfoldings or recurrent loop abnormalities or tomacula with myelin breakdown
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• at P14, focal hypermyelination is observed in the sciatic nerve
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• at P60, stimulation at proximal sites in the sciatic nerve results in flattened potential peaks, significantly decreased nerve conduction velocity (NCV), and severely reduced amplitudes of the compound action potentials (CAPs) in the sciatic nerve, indicating severe axonal damage
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• at P60, mice exhibit a significant reduction in nerve conduction velocity (NCV) in the sciatic nerve
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homeostasis/metabolism
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• at P60, mice exhibit a significant reduction in treadmill lane distance in a treadmill assay
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