Genetic and functional analysis of the otosclerosis-like condition of the LP/J mouse.

The LP/J mouse is the only available genetic model for otosclerosis. The otosclerosis-like condition of the LP/J mouse resembles the human condition in several ways, although there are differences in the two species in the most common locus of the dysplastic otic lesions. The mouse model would be more useful if its auditory dysfunction and genetic inheritance could also be compared with the human disease. Matings of the otosclerosis-like LP/J and the normal CBA/J inbred mice were used to generate F1 and backcross generations. The F1 showed neither functional (electrocochleographic) nor anatomical abnormalities, indicating a recessive nature of the mouse genetic disease. This is in contrast to some reports of dominance (with incomplete penetrance) of otosclerosis in humans. No evidence of X-chromosome-linked genetic influence was found in the mouse, in agreement with the human condition. These interpretations were confirmed in tests of the backcross of the F1 to the CBA/J parental genotype (BC). The anatomical and functional abnormalities were present in some of the backcrosses of the F1 to the LP/J parental genotype (BL). A comparison of bone-conducted and air-conducted electrocochleographic responses provided evidence for both conductive and sensorineural losses in the LP/J and BL mice.