Cochlear developmental defect and background-dependent hearing thresholds in the Jackson circler (jc) mutant mouse

Jackson circler (jc) is a spontaneous, recessive mouse mutation that results in circling behavior and an impaired acoustic startle response. In this study, we refined the phenotypic and genetic parameters of the original jc mutation and characterized a new mutant allele, jc(2J). In open-field behavior tests, homozygous jc mutants exhibited abnormal circling and ambulatory behavior that was indistinguishable from that of phenotypically similar mutants with defects in the vestibule of the inner ear. The jc/jc and jc(2J)/jc(2J) mice had stable elevated auditory-evoked brainstem response (ABR) thresholds at the 16kHz stimulus of 88+/-9dB sound pressure levels (SPL) and 43+/-11dB SPL, respectively. Peak latencies and peak time intervals were normal in jc mutants. The jc mice showed no measurable distortion-product otoacoustic emissions (DPOAEs) above the system noise floor. In the mutant cochlea, the apical turn failed to form due to the developmental growth arrest of the cochlear duct at the level of the first turn at gestational day 13.5. In a large intrasubspecific intercross, jc localized to a 0.2cM interval at position 25cM on chromosome 10, which is homologous to the human 6q21 region. On CZECHII/Ei and CAST/Ei backgrounds jc/jc mutant hearing thresholds at the 16kHz stimulus were significantly lower than those observed on the C57BL/6J background, with means of 62+/-22dB SPL and 55+/-18dB SPL, respectively. Genome-wide linkage scans of backcross, intercross, and congenic progeny revealed a complex pattern of genetic and stochastic effects.