ABNORMAL NERVE-CONDUCTION STUDIES IN MICE EXPRESSING A MUTANT FORM OFTHE POU TRANSCRIPTION FACTOR SCIP

We have previously described transgenic mice that harbor a dominant-ne gative antagonist of the POU protein SCIP (termed Delta SCIP). Native SCIP is expressed in promyelinating Schwann cells, where it represses expression of the myelin structural genes, The Delta SCIP mice display morphologic and behavioral abnormalities, including decreased axonal diameter, increased myelin thickness, developmentally early myelinatio n, and clinical features of neuropathy, To assess the neurophysiologic correlates of these abnormalities, a series of electrophysiologic tes ts was performed, Despite having smaller diameter axons, mice expressi ng the Delta SCIP transgene had similar maximum conduction velocities in caudal, sural, and tibial nerves compared to wild-type controls, Th erefore, conduction in Delta SCIP animals was faster than predicted by axon diameter alone, Compound amplitude responses were 38% higher in the Delta SCIP caudal nerve, Delta SCIP 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 Del ta SCIP phenotype, In addition, these studies address the physiologic sequelae of altering the g-ratio in the absence of demyelination or ax onal degeneration. (C) 1997 Wiley-Liss, Inc.