• severe deficits in balance and coordination by P14

• marked hyperactivity by 5-6 weeks

• incomplete cavitation of the organ of Corti at P0

• at P0, IHCs and OHCs in the organ of Corti fail to show early signs of differentiation

• by P14, no hair cells are identified in the organ of Corti

• at P0, IHCs in the organ of Corti fail to show early signs of differentiation, including growth of stereocilia and segregation of cell nuclei to a plane above the level of supporting cell nuclei

• at P0, OHCs in the organ of Corti fail to show early signs of differentiation, including growth of stereocilia and segregation of cell nuclei to a plane above the level of supporting cell nuclei

• by P14, many of the normal supporting cell populations are absent in the organ of Corti

• at P0, no hair cells are identified in the sensory epithelia of the maculae and the cristae; the row of nuclei above the supporting cell nuclei is poorly organized

• at P0, stereocilia bundles are absent in the sensory epithelia of the maculae and the cristae

• at P42, mice exhibit a complete failure of click-evoked ABRs to stimuli up to 80 dB above normal threshold

• complete deafness by P42

• at P0, IHCs and OHCs in the organ of Corti fail to show early signs of differentiation

• by P14, no hair cells are identified in the organ of Corti

• at P0, IHCs in the organ of Corti fail to show early signs of differentiation, including growth of stereocilia and segregation of cell nuclei to a plane above the level of supporting cell nuclei

• at P0, OHCs in the organ of Corti fail to show early signs of differentiation, including growth of stereocilia and segregation of cell nuclei to a plane above the level of supporting cell nuclei

• at P0, no hair cells are identified in the sensory epithelia of the maculae and the cristae; the row of nuclei above the supporting cell nuclei is poorly organized

• at P0, stereocilia bundles are absent in the sensory epithelia of the maculae and the cristae

• at P0, the cochlea and spiral ganglion appear grossly normal

• however, most spiral ganglion cells degenerate by P14

• complete degeneration of vestibular ganglion by P14, with absence of calycial endings surrounding type I hair cells

• in response to hypergravity (2G), homozygotes fail to exhibit the expected reduction in circadian rhythm amplitude which normally lasts for ~7 days

• at 1 month of age, homozygotes display hyperactivity

• at 1 month of age, homozygotes tend to circle

• at 6 weeks, the organ of Corti contains undifferentiated supporting cells with the exception of some pillar cells

• at 6 weeks, the Rosenthal canal, which contains the spiral ganglion, appears to be smaller than normal

• the channels in the bone in the osseus spiral lamina are also reduced

• at 18 months, the basilar membrane may totally lack cells in the basal turn, while the middle and apical turns contain cells with few organelles

• at 6 weeks, homozygotes display absence of hair cells in the organ of Corti

• however, the tectorial membrane appears to be unaffected by the absence of hair cells or the disruption of the organ of Corti

• by 18 months, supporting cells show complete degeneration in some areas

• at 18 months, homozygotes display severe degeneration of the organ of Corti

• at 18 months, the stria vascularis is normal except in the extreme apex where it is thin and degenerated

• at 5-7 weeks of age, homozygotes are deaf

• at 6 weeks, homozygotes display absence of hair cells in the organ of Corti

• however, the tectorial membrane appears to be unaffected by the absence of hair cells or the disruption of the organ of Corti

• at 18 months, the spiral ganglion consists of a few neurons and myelinated fibers although these lack hair cell targets

• at 6 weeks, homozygotes show a significant reduction in the number of spiral ganglion cells in the middle cochlear turn; the basal and apical turns are not as affected

• by 18 months, homozygotes show severe degeneration of the spiral ganglion cells

• in response to hypergravity (2G exposure), homozygotes lack a normal autonomic response i.e. a dramatic drop in body temperature and concomitant circadian adjustment

• however, no differences in mean daily temperature and circadian rhythm amplitude are noted after chronic 2G (2 wks) or during the 1G recovery relative to wild-type littermates

• in addition, unlike wild-type mice, homozygotes show virtually no increase in neuronal activity (i.e. Fos induction) in the vestibular complex and parabrachial nucleus after 2G exposure

• only minor numbers of 2G-induced Fos immunoreactive neurons are detected, mainly in the nucleus of solitary tract (NST) and the central nucleus of amygdala (CNA), suggesting an intact afferent vagal component

• in response to hypergravity, homozygotes fail to exhibit the expected dramatic fall in mean body temperature immediately after exposure to 2G

• at 6 weeks, the organ of Corti contains undifferentiated supporting cells with the exception of some pillar cells

• at 2, 18 and 24 months of age, heterozygotes exhibit a comparable hearing to wild-type mice, with similar patterns of cochlear degeneration (J:57149)

• both heterozygous and wild-type mice display a ~30 dB hearing loss beginning at 18 months of age, outer hair cell degeneration and loss of spiral ganglion neurons in the basal turn (J:57149)