Abnormal nerve conduction studies in mice expressing a mutant form of the POU transcription factor SCIP.
We have previously described transgenic mice that harbor a dominant-negative antagonist of the POU protein SCIP (termed deltaSCIP). Native SCIP is expressed in promyelinating Schwann cells, where it represses expression of the myelin structural genes. The deltaSCIP mice display morphologic and behavioral abnormalities, including decreased axonal diameter, increased myelin thickness, developmentally early myelination, and clinical features of neuropathy. To assess the neurophysiologic correlates of these abnormalities, a series of electrophysiologic tests was performed. Despite having smaller diameter axons, mice expressing the deltaSCIP transgene had similar maximum conduction velocities in caudal, sural, and tibial nerves compared to wild-type controls. Therefore, conduction in deltaSCIP animals was faster than predicted by axon diameter alone. Compound amplitude responses were 38% higher in the deltaSCIP caudal nerve. DeltaSCIP tibial F-wave responses showed less difference between minimum and maximum latencies than controls, suggesting less variance between fastest and slowest conducting fibers. These data further characterize the functional components of the deltaSCIP phenotype. In addition, these studies address the physiologic sequelae of altering the g-ratio in the absence of demyelination or axonal degeneration.
Bieri
P L
PL
Department of Neurology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Arezzo
J C
JC
Weinstein
D E
DE
D000818:Animals; D005071:Evoked Potentials; D051379:Mice; D008822:Mice, Transgenic; D009412:Nerve Fibers / Q000502:physiology / Q000648:ultrastructure; D009413:Nerve Fibers, Myelinated / Q000502:physiology / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009431:Neural Conduction / Q000235:genetics*; D050816:Octamer Transcription Factor-6; D010525:Peripheral Nerves / Q000002:abnormalities / Q000502:physiology* / Q000648:ultrastructure; D013497:Sural Nerve / Q000502:physiology; D013623:Tail / Q000294:innervation; D013979:Tibial Nerve / Q000502:physiology; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
D009419:Nerve Tissue Proteins; C494180:Pou3f1 protein, mouse; D014157:Transcription Factors; D050816:Octamer Transcription Factor-6