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Abstract: In the mammalian nervous system, axons are commonly surrounded by myelin, a lipid-rich sheath that is essential for precise and rapid conduction of nerve impulses. In the peripheral nervous system (PNS), myelin sheaths are formed by Schwann cells which wrap around individual axons. While the tyrosine kinase receptors ERBB2 and ERBB3 are established mediators of peripheral myelination, less is known about the functions of the related epidermal growth factor receptor (EGFR) in the regulation of PNS myelination. Here, we report a peripheral neurodegenerative disease caused by increased EGFR activation. Specifically, we characterize a symmetric and distally pronounced, late-onset muscular atrophy in transgenic mice overexpressing the EGFR ligand epigen. Histological examination revealed a demyelinating neuropathy and axon degeneration, and molecular analysis of signaling pathways showed reduced protein kinase B (PKB, AKT) activation in the nerves of Epigen-tg mice, indicating that the muscular phenotype is secondary to PNS demyelination and axon degeneration. Crossing of Epigen-tg mice into an EGFR-deficient background revealed the pathology to be completely EGFR-dependent. This mouse line provides a new model for studying molecular events associated with early stages of peripheral neuropathies, an essential prerequisite for the development of successful therapeutic interventions. [Copyright &y& Elsevier]

Abstract: The value of avian models in peripheral nerve research recently became substantiated by the immunobiological similarity of avian inflammatory demyelinating polyradiculoneuropathy to human Guillain–Barré syndrome providing an alternative animal model for experimental autoimmune neuritis. As electrophysiologic evaluation of nerve roots is essential part of the diagnosis of polyradiculoneuropathies in humans, it would be favourable to have similar research methods available for juvenile chickens. Hence, this study was performed (1) to establish a tool-set that allows for reproducible evaluation of the tibial/sciatic nerve and its nerve roots, (2) to achieve age-matched reference values, and (3) to trace the kinetics of peripheral nerve maturation within chickens. Nine chickens underwent serial electrodiagnostic examinations between the age of 6 and 15 weeks. Several methods of sensory and motor nerve fiber stimulation of the tibial/sciatic nerve were tested and modified or established. Ultimately, scalp-recorded somatosensory evoked potentials, compound muscle action potentials elicited by tibial/sciatic nerve electrical as well as spinal magnetic stimulation and motor nerve conduction velocity were available for tibial/sciatic nerve and nerve root evaluation in chickens. Base values were obtained for all investigations and parameters. Results indicated that the maturation of the nerve fibers is incomplete up to the age of 15 weeks. The methods tested here provide an excellent tool-set for quantitative tibial/sciatic nerve and nerve root assessment in avian polyradiculoneuropathies, especially within the scope of longitudinal monitoring of the disease course. [ABSTRACT FROM AUTHOR]