B6 x STOCK Nox3^het/J

Stock number: 000061
Research areas: Internal/Organ Research, Neurobiology Research, Sensorineural Research

Detailed description

Head tilt (Nox3^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. Nox3^het/Nox3^het mutants are unable to sense orientation under water and therefore, cannot swim properly. If held by the tail, Nox3^het/Nox3^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, Nox3^het/Nox3^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 Nox3^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 Nox3^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)

Development

The Nox3^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 Nox3^het/Nox3^het (F27) was outcrossed once to the F1 hybrid C3B6A/A^w-J to separate Nox3^het from downless Jackson (Edar^dl-J) and grey lethal (gl). The strain was maintained by sibling mating thereafter. In 1983, embryos derived from homozygous F30 C3B6A/A^w-J-Nox3^het males crossed to C57BL/6J dams were cryopreserved. gl and Edar^dl-J have not been detected in the stock since F2.

Allele

Symbol: Nox3^het
Name: head-tilt
MGI accession ID: MGI:1856606
Generation method: Spontaneous
Marker symbol: Nox3
Marker name: NADPH oxidase 3
Chromosome: 17
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.