Mice homozygous for the Otop1tlt mutation are viable and fertile. They can be identified outwardly by a tilt in the head posture, which is reported to be detectable in 50-75% of homozygotes. Auditory brainstem responses at four months of age are normal. Although these mice are not deaf and do not show degeneration of the cochlea or vestibular organs, most completely lack otoconia in both the utricle and saccule and thus have problems with spatial orientation. A few giant otoconia have been observed infrequently in a small minority of these mutants, but generally there is agenesis of otoconia. The macular epithelium and otolithic membrane are intact despite the lack of otoconia. Homozygotes are unable to orient themselves in water to find the surface and thus are categorized as non-swimming since they would drown without rescue. Approximately 2% of these homozygotes are able to find the water surface despite somersaults, backflips, or other abnormal motions indicative of failed perception of gravity. Penetrance of the Otop1tlt mutation is reported to be nearly 100% although there is some variation in expressivity. 2D-PAGE of sensory epithelium and otoconial membrane from Otop1tlt homozygotes fails to detect otoconin 90, the principal otoconial matrix protein. (Lane 1986 and 1987; Ornitz et al., 1998; Hurle et al., 2001 and 2003.)
The recessive tlt mutation arose spontaneously in 1983 on the STOCK p6H/pd background in the laboratory of Eva Eicher at The Jackson Laboratory. Otop1tlt was backcrossed onto the C57BL/6J background via backcross-intercross. In 1986 C57BL/6J females were bred to homozygous males at NE5F1 and the resulting embryos were cryopreserved.
|Allele Synonym(s)||tilted head; tlt|
|Gene Symbol and Name||Otop1, otopetrin 1|
|Strain of Origin||STOCK Oca2p-6H/Oca2p-d|
|Molecular Note||The mutation in the tlt mouse has been identified as a C-to-A transversion at coding nucleotide 452 in the third exon of the gene. This results in a alanine to glutamic acid change at amino acid position 151 (p.A151E).|