A Novel Model for the Study of Peripheral-Nerve Regeneration Following Common Nerve Injury Paradigms

Recent advances in molecular neurobiology include the development of transgenic mice that express genes encoding fluorescent proteins under neuron-specific promoters (XFP mice). These mice have been used in the field of developmental neurobiology, but use has expanded to include the study of peripheral-nerve axonal regeneration subsequent to crush or unrepaired transection injuries. This report presents a transgenic mouse, which differs from previously reported and commercially available mice, in that enhanced yellow fluorescent protein expression (EYFP) is driven by the human thy1 promoter (hThy1). Motor and sensory peripheral nerves in these mice appear a bright yellow-green under fluorescent microscopy. This study tracks nerve regeneration in live animals using a serial imaging system. It also introduces a novel model for examining the clinically relevant nerve-injury paradigms of tibial nerve transection repaired with primary neurorrhaphy or graft, and end-to-side neurorrhaphy. Live-animal serial nerve imaging is compared with wet-mount fluorescent microscopy and histomorphometry in the same nerve specimens. The use of transgenic mice that strongly express EYFP in their peripheral neurons, coupled with serial nerve imaging, provide an important methodology for studying the heterogeneous nature of axonal elongation following peripheral-nerve injuries.

KEYWORDS

Yellow fluorescent protein - neurorrhaphy - serial imaging - transgenic mice

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