Lack of Effects of Transforming Growth Factor-α Gene Knockout on Peripheral Nerve Regeneration May Result from Compensatory Mechanisms

• Published in: Experimental neurology Vol. 172; no. 1; pp. 182 - 188
• Main Authors: Xian, Cory J., Li, Li, Deng, Yan-Shen, Zhao, Su-Ping, Zhou, Xin-Fu
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.11.2001; Elsevier
• Subjects: Amphiregulin; Animals; Axons - physiology; Biological and medical sciences; Cell Count; Development. Senescence. Regeneration. Transplantation; Disease Models, Animal; EGF family; EGF Family of Proteins; Fundamental and applied biological sciences. Psychology; Ganglia, Spinal - cytology; Ganglia, Spinal - physiology; Gene Expression - physiology; Glycoproteins - biosynthesis; Glycoproteins - genetics; Growth Substances - biosynthesis; Growth Substances - genetics; injury; Intercellular Signaling Peptides and Proteins; Ligands; Male; Mice; Mice, Knockout; Motor Neurons - cytology; Motor Neurons - physiology; Nerve Crush; Nerve Fibers, Myelinated - physiology; Nerve Regeneration - physiology; Neurons, Afferent - cytology; Neurons, Afferent - physiology; peripheral nerve; Peripheral Nerve Injuries; Peripheral Nerves - physiology; Receptor, Epidermal Growth Factor - biosynthesis; Receptor, Epidermal Growth Factor - genetics; redundancy; regeneration; RNA, Messenger - analysis; RNA, Messenger - biosynthesis; Sciatic Nerve - injuries; Sciatic Nerve - physiology; Spinal Cord - cytology; Spinal Cord - physiology; TGF-α; Transforming Growth Factor alpha - deficiency; Transforming Growth Factor alpha - genetics; Up-Regulation - physiology; Vertebrates: nervous system and sense organs; EGF family; redundancy; injury; peripheral nerve; regeneration; TGF-α; Peripheral nerve; Spinal cord; Transforming growth factor; Rodentia; Central nervous system; Myelinated nerve fiber; Posterior spinal root; Dorsal ganglion; Motor neuron; Survival; Ganglion neuron; Regeneration; Vertebrata; Mammalia; Epidermal growth factor; Mouse; Animal; Sensory nerve; Sensory neuron; Transforming growth factor α; Motor nerve; Sciatic nerve; Growth factor
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1006/exnr.2001.7771

Transforming growth factor-α (TGF-α), previously identified as a major member of the epidermal growth factor (EGF) family of growth factors, plays a role in proliferation, differentiation, and survival of neuronal and glial precursors and is implicated in development of the nervous system. However, its roles in nerve injury-induced responses remain obscure. The current study examined roles of endogenous TGF-α in peripheral nerve regeneration using sciatic nerve injury models with TGF-α knockout mice. Three weeks after a sciatic nerve crush, no significant differences were found between TGF-α wild-type and mutant mice in the number of retrogradely labeled L5 dorsal root ganglion (DRG) sensory neurons and L5 spinal cord motor neurons and in the morphology of myelinated regenerating nerve fibers, indicating that TGF-α is not essential for sensory and motor nerve regeneration. To assess a possible functional redundancy among TGF-α-related ligands in response to a nerve injury, mRNA expression of the EGF family was analyzed by RT-PCR in L4/L5 DRG pools and distal degenerating sciatic nerve segments after sciatic nerve ligation. Prior to and 1 day after ligation, there was a higher level of EGF-R mRNA in DRGs and in nerve in TGF-α null mice compared to wild types, and there was an induction of ligand amphiregulin mRNA in DRGs in mutant mice in place of the TGF-α upregulation present in wild types. These results indicate that TGF-α gene knockout does not affect peripheral nerve regeneration, probably due to a functional redundancy within the EGF family through a compensatory expression mechanism at both the receptor and ligand levels in TGF-α knockout mice.