Partial behavioral compensation is revealed in balance tasked mutant mice lacking otoconia

We describe for the first time behavioral tests which show that mammals with congenital absence of otoconia can learn a motor task that normally relies on gravity perception. The mouse mutation tilted (tlt) occurs in the otopetrin 1 gene (Otop1 ^tlt/tlt) and eliminates an essential component necessary for the formation of otoconia. Our data show that even in the absence of otoconia, tlt mutant mice, like normal mice, learn to cross a bar suspended between two boxes and, with practice, improve their speed of crossing. Despite this learned compensatory skills, tlt mutant mice show balance impairments, such as falling from the bar, not observed in wild type (WT) or heterozygous (het) Otop1 ^+/tlt littermates. The tlt mutant mice also use their tail as additional support, a behavior that is rarely exhibited in the control littermates. Interestingly, the Otop1 ^+/tlt heterozygous littermates show in many aspects an intermediate phenotype between wild type and tlt mutant mice, suggestive of a gene dosage effect. Overall, these data support the notion that mammals can use other otic and extraotic receptors such as semicircular canals and limb proprioreceptors, respectively, to compensate for the absence of otoconia-mediated gravity perception in a balance task.