Biological Analysis of a New Spontaneous Mutant Mouse Showing Deafness and Circling Behavior / 대한이비인후과학회지

ABSTRACT

BACKGROUND AND OBJECTIVES: Deafness is the most common sensory deficit and hereditary defect in human populations. The present study investigated the causative gene in circling mice using the complementation test. In addition, the phenotypes and histopathologic findings in circler mice, spinner mice, and compound heterozygote mice were analyzed to elucidate the mechanism of causative gene in inner ear deafness. MATERIALS AND METHOD: In order to analyze inner ear pathology in time sequence for the circler mice, spinner mice, and compound heterozygote, five groups of the homozygous mutants of different ages were used 10, 18, 21, 35, and 90 days old. The organs of Corti and spiral ganglion neurons in the basal and middle turns were included for quantification. For the preparation of genomic DNA, tail tissues were used. RESULTS: The hair cells in the organ of Corti degenerated in a time-dependent manner. In the basal and middle turns, the volume ratio of spiral ganglion neurons significantly decreased as the mutant aged. RT-PCR analysis indicated that transmembrane inner ear (Tmie) was absent in the case of circler mice, similar to spinner mouse of which is defective Tmie gene. Therefore the variations may be a result from strain-specific allelic differences of the Chr 9 Tmie gene itself (allelic heterogeneity). CONCLUSION: The cir mutant is a suitable mouse model for neuroepithelial defects. PCR and RT-PCR analyses suggest that the Tmie transcript is absent in circler mice. This model represents another candidate for human genetic hearing loss.