Malformation and Degeneration in the Inner Ear of MOS Transgenic Mice

Abstract

Transgenic mice carrying the mos proto-oncogene linked to a retroviral transcriptional control sequence display behavioral abnormalities including circling, hyperactivity, head tilt, and bobbing. Axonal degeneration, neuronal chromatolysis, spongiform encephalopathy, gliosis, and inflammatory infiltrates are reportedly found in the central nervous systems of all mutants with the behavioral traits. Hearing was tested by means of broadband free-field rarefaction clicks with auditory brain stem response recorded between vertex and mouth electrodes. No detectable auditory response was elicited in transgenic animals, in contrast to five distinct positive peaks observed in littermate control animals. Light microscopic survey of temporal bone histopathology in mutants revealed extensive degeneration of the organ of Corti with loss of hair cells in all cochlear turns and loss of supporting cells and atrophy of spiral ganglion cells. The spiral Iimbus was deformed, with replacement of the usual convexity of the superior surface by a flattened trough configuration. Hair cells of the vestibular end organs appeared normal. Pathologic alteration in levels of mos transgene RNA appears to have a direct effect on the structural integrity of the inner ear.