Head tilt (het) is an autosomal recessive mutation that can cause abnormal circling behavior and hyperactivity in affected mice. Homozygotes also exhibit a subtle head tilt. Together, the abnormal behavioral phenotype is consistent with that of a vestibular disorder. Evoked auditory brainstem response profiles are normal indicating that the mutants are not deaf. het/het mutants are unable to sense orientation under water and therefore, cannot swim properly. If held by the tail, het/het mice retract, rather than extend, their limbs; they also flex ventrally, instead of dorsally as wild type mice do. When lowered quickly by the tail, het/het mice fail to extend their forelimbs in a normal manner and have difficulty righting themselves if dropped vertically from a short distance. Morphological assessment of the inner ear of homozygotes reveals an abnormal appearance of the saccule and utricle owing to a complete absence of otoliths. Otoliths are tiny calciferous granules within the statoconic membrane that covers the sensory epithelia of the acoustic maculae. These ear crystals function as mass particles that stimulate gravity receptors in the maculae of the utricle and saccule in response to head tilting and gravitational forces. Electrophysiological assessment of the vestibular neurons in the het mutants demonstrates these cells totally lack vestibular evoked potentials in response to pulsed linear acceleration. Thus, the mutants are unable to process ostolite-mediated sensory stimuli throughout their entire lifespan. The het gene product is likely involved in the formation of the otolithic ear crystals (prior to embryonic day 14), perhaps through the regulation of calcium secretion by neuroepithelial cells. Structures of the cochlea and middle ear appear normal and melanocyte function is not compromised. (Sweet, 1980; Bergstrom et al., 1998; Jones et al., 1999)
The het mutation arose spontaneously at The Jackson Laboratory in 1975 in the GL/Le inbred strain (Stock No. 000255) which was then at F25. In 1976, a male het/het (F27) was outcrossed once to the F1 hybrid C3B6A/Aw-J to separate het from downless Jackson (Edardl-J) and grey lethal (gl). The strain was maintained by sibling mating thereafter. gl and Edardl-J have not been detected in the stock since F2. The het mutation was backcrossed from the C3B6-A/Aw-J background onto C57BL/6JEi reaching N10F14+N2F12 in 2002.
|Gene Symbol and Name||Nox3, NADPH oxidase 3|
|Strain of Origin||GL/Le|
|Molecular Note||The mutation in the het mouse was identified as retroviral insertion into intron 12, resulting in aberrant splicing.|
When using the head-tilt mouse strain in a publication, please cite the originating article(s) and include JAX stock #002557 in your Materials and Methods section.