Vestibulocochlear defects and effects of deuterium oxide in mutant bustling (BUS) mice

Bustling mouse (BUS/Idr: bus) is a mutant mouse strain which exhibits bustling/hyperkinetic behavior and functional disorders related to the vestibulocochlear system such as rapid circling and loss of auditory startling response. In homozygous (bus/bus) mice this phenotype develops progressively after birth and has been shown from cross experiments to be inherited by a single autosomal recessive gene. Using light and electron microscopy, we examined the development of pathological changes in the inner ear of homozygous mice. Effects of deuterium oxide, which has been shown to influence vestibular function, on the abnormal behavior of homozygous mice of different ages were also examined. Pathological changes of the inner ear including impairment and/or loss of auditory hair cells, deformation and/or loss of the inner and outer tunnels of the organ of Corti, hypoplasia of the otoliths, and decrease in number of neurons of the spiral genglion were observed in the homozygous mice starting before the weaning stage and progressively thereafter, but not in the heterozygous mice. Although histological changes were also noted in the crista ampullaris and maculae, they were less evident than those in the cochlea at least until the mice were 6 weeks old. Administration of deuterated physiological saline (8-16 ml/kg, per os) tended to decrease the abnormal behavior of the homozygous mice, including rapid circling. These morphological and functional findings suggest that BUS mice may be a useful model for analysis of the pathogenesis of vestibulo-cochlear disorders.