hearing/vestibular/ear phenotype

• increased susceptibility to noise-induced hearing loss
  • Normal - however, ABR thresholds of wild-type and heterozygous mutant siblings are indistinguishable prior to noise-exposure
  (MGI Ref ID J:108881)
  • at 15 days following an 8 hr, 113 dB noise exposure, heterozygotes exhibit significant permanent threshold shifts at 16 and 32 kHz ABR stimuli that are 15 or 25 dB higher than those of wild-type littermates
  (MGI Ref ID J:108881)

hearing/vestibular/ear phenotype

• increased susceptibility to age-related hearing loss
  • Background Sensitivity - backcrossing to the C3H/HeJ inbred strain, which does not undergo age-related hearing loss (AHL) by 3 months, does not eliminate the AHL phenotype; hence, these mice are not used for noise-induced hearing loss experiments
  (MGI Ref ID J:108881)
  • Background Sensitivity - backcrossing to the CAST/Ei strain eliminates AHL, as shown by similar ABR thresholds at 3 months and 6-7 months relative to age-matched wild-type littermates
  (MGI Ref ID J:108881)

• increased or absent threshold for auditory brainstem response
  • at 3 months, heterozygous offspring of 129/Black Swiss x C3H F1 and (129/Black Swiss x C3H) x C3H N2 exhibit ABR thresholds that are 60 dB and 20-40 dB, respectively, higher than those of wild-type mice
  (MGI Ref ID J:108881)
  • Background Sensitivity - backcrossing to the C3H/HeJ inbred strain does not reduce the elevated ABR thresholds; in contrast, ABR thresholds of heterozygous F1 offspring of 129/Black Swiss x CAST/Ei matings are within 5 dB of wild-type littermates
  (MGI Ref ID J:108881)

hearing/vestibular/ear phenotype

• abnormal organ of Corti morphology
  • Normal - however, heterozygotes do not display any overt manifestations of an abnormal phenotype or altered cerebellum morphology
  (MGI Ref ID J:48863)
  • at 5-6 weeks, heterozygotes show a range of histopathology in the cochlear ducts, despite normal otoconial numbers
  (MGI Ref ID J:48863)

• increased or absent threshold for auditory brainstem response
  • at 5-6 weeks of age, heterozygotes show significantly elevated ABR thresholds (~70-80 db) in response to broad band click and 3-ms pure tones of 8, 16, and 32 kHz relative to wild-type thresholds (~30-45 db)
  (MGI Ref ID J:48863)

• impaired hearing
  • at 5-6 weeks of age, heterozygotes display a severe hearing loss
  (MGI Ref ID J:48863)

hearing/vestibular/ear phenotype

• abnormal inner ear morphology
  (MGI Ref ID J:48863)

• absent otoliths
  • homozygotes lack otoconia in both the saccule and utricle
  (MGI Ref ID J:48863)
  • Normal - however, hair cells, support cells, and innervation of the sensory epithelium in the utricle and saccule are normal, and the otolithic membrane is present above the macula in each chamber
  (MGI Ref ID J:48863)
  • Normal - in addition, the semicircular canals, and the crista ampullaris, with its sensory hair cells and gelatinous cupula within the ampulla of each duct, are normal
  (MGI Ref ID J:48863)

• decreased cochlear hair cell number
  • at 5-6-weeks of age, the number of cochlear IHCs and OHCs is reduced in affected regions of the cochlear duct
  (MGI Ref ID J:48863)

• increased or absent threshold for auditory brainstem response
  • wild-type mice show a typical ABR waveform at 40-70 db after exposure to a 0.1-ms broad band click; in contrast, all homozygotes fail to exhibit a detectable ABR waveform even at 99 db
  (MGI Ref ID J:48863)

• sensorineural hearing loss
  (MGI Ref ID J:48863)

• abnormal hair cell mechanoelectric transduction
  • organotypic cultures of cochleae from P0-P3 mice (studied at P1-P4) indicate that, although the amplitude and kinetics of transduction currents in mutant OHCs obtained from the first row of the mid-apical turn are qualitatively similar to those of wild type controls, the curves relating bundle displacement (X) to channel opening probability, P_open (X) are shifted positively with respect to controls
  (MGI Ref ID J:119503)
  • this shift is more pronounced in Atp2b2^tm1Ges mice (175 nm) than in Atp2b2^dfw mice (117 nm)
  (MGI Ref ID J:119503)
  • pe controls, the curves relating bundle displacement (X) to channel opening probability, P_open (X) are shifted positively with respect to controls
  (MGI Ref ID J:119503)

• abnormal vestibular hair cell physiology
  • as a result, the Ca²⁺ clearing rate of stereocilia is decreased and therefore similar to the slower rate of cell soma
  (MGI Ref ID J:119503)
  • in organotypic utricular cultures from P0-P3 mice (studied at P1-P4), Ca²⁺ imaging of vestibular hair cells indicates that dissipation of stereociliary Ca²⁺ transients induced by Ca²⁺ uncaging is compromised
  (MGI Ref ID J:119503)

• deafness
  • at 5-6-weeks of age, homozygotes are profoundly deaf
  (MGI Ref ID J:48863)
  • homozygotes are congenitally and profoundly deaf
  (MGI Ref ID J:108937)

• absent distortion product otoacoustic emissions
  • at 4-6 months, homozygotes fail to produce any significant DPOAEs over a geometric-mean frequency range from 5.6-48.5 kHz compared with wild-type mice
  (MGI Ref ID J:108937)

• absent tunnel of Corti
  • at 5-6-weeks of age, the tunnel of Corti varies in regions of the cochlear duct from wide to greatly reduced or absent
  (MGI Ref ID J:48863)

• absent organ of Corti supporting cells
  • at 5-6-weeks of age, supporting cells may be entirely absent in severely affected regions of the cochlear duct
  (MGI Ref ID J:48863)

• decreased organ of Corti supporting cell number
  • at 5-6-weeks of age, the number of supporting cells may be reduced in affected regions of the cochlear duct
  (MGI Ref ID J:48863)

• abnormal cochlear hair cell physiology
  • in organotypic cochlear cultures, the sensitivity of mechanoelectrical transduction channels to hair bundle displacement in outer cochlear hair cells is reduced
  (MGI Ref ID J:119503)

• abnormal inner ear vestibule morphology
  (MGI Ref ID J:48863)

• absent cochlear hair cells
  • at 5-6-weeks of age, cochlear IHCs and OHCs may be entirely absent in severely affected regions of the cochlear duct
  (MGI Ref ID J:48863)

• absent pillar cells
  • at 5-6-weeks of age, the number of pillar cells may be reduced or entirely absent in severely affected regions of the cochlear duct
  (MGI Ref ID J:48863)

• abnormal organ of Corti morphology
  • r cells
  (MGI Ref ID J:48863)
  • at 5-6-weeks of age, homozygotes show a variable architecture ranging from a small tunnel of Corti with identifiable hair cells, pillar cells, and other cell types to complete absence of a tunnel or clearly identifiable support cells, pillar cells, or hair cells
  (MGI Ref ID J:48863)

• abnormal auditory brainstem response
  (MGI Ref ID J:108937)

behavior/neurological phenotype

• ataxia
  • homozygotes grow to adulthood but show severe ataxia that is evident at P12
  (MGI Ref ID J:48863)

• impaired balance
  • young homozygotes fail to maintain their balance when walking or standing and frequently fall onto their sides
  (MGI Ref ID J:48863)
  • by 5 months of age, homozygotes improve in their ability to maintain an upright position, and many tend to alternately hyperextend and clench their rear legs and feet
  (MGI Ref ID J:48863)

• abnormal reflex
  • homozygotes fail to respond to a hand clap
  (MGI Ref ID J:48863)

• impaired righting response
  • older homozygotes often roll onto their backs and flail their hind legs and tail while attempting to right themselves
  (MGI Ref ID J:48863)

• abnormal gait
  • homozygotes exhibit an unsteady gait
  (MGI Ref ID J:48863)

homeostasis/metabolism phenotype

• abnormal calcium ion homeostasis
  • in organotypic utricular cultures from P0-P3 mice, Ca²⁺ imaging of vestibular hair cells indicates that dissipation of stereociliary Ca²⁺ transients induced by Ca²⁺ uncaging is compromised
  (MGI Ref ID J:119503)
  • in the inner ear, sensory hair cells show abnormal calcium homeostasis due to absence of otoconia
  (MGI Ref ID J:108937)

nervous system phenotype

• abnormal auditory cortex morphology
  (MGI Ref ID J:108937)

• decreased cochlear hair cell number
  • at 5-6-weeks of age, the number of cochlear IHCs and OHCs is reduced in affected regions of the cochlear duct
  (MGI Ref ID J:48863)

• abnormal vestibular hair cell physiology
  • as a result, the Ca²⁺ clearing rate of stereocilia is decreased and therefore similar to the slower rate of cell soma
  (MGI Ref ID J:119503)
  • in organotypic utricular cultures from P0-P3 mice (studied at P1-P4), Ca²⁺ imaging of vestibular hair cells indicates that dissipation of stereociliary Ca²⁺ transients induced by Ca²⁺ uncaging is compromised
  (MGI Ref ID J:119503)

• abnormal hair cell mechanoelectric transduction
  • this shift is more pronounced in Atp2b2^tm1Ges mice (175 nm) than in Atp2b2^dfw mice (117 nm)
  (MGI Ref ID J:119503)
  • organotypic cultures of cochleae from P0-P3 mice (studied at P1-P4) indicate that, although the amplitude and kinetics of transduction currents in mutant OHCs obtained from the first row of the mid-apical turn are qualitatively similar to those of wild type controls, the curves relating bundle displacement (X) to channel opening probability, P_open (X) are shifted positively with respect to controls
  (MGI Ref ID J:119503)
  • pe controls, the curves relating bundle displacement (X) to channel opening probability, P_open (X) are shifted positively with respect to controls
  (MGI Ref ID J:119503)

• thin cerebellar molecular layer
  (MGI Ref ID J:48863)

• abnormal cerebellum morphology
  (MGI Ref ID J:48863)

• abnormal cochlear hair cell physiology
  • in organotypic cochlear cultures, the sensitivity of mechanoelectrical transduction channels to hair bundle displacement in outer cochlear hair cells is reduced
  (MGI Ref ID J:119503)

• absent cochlear hair cells
  • at 5-6-weeks of age, cochlear IHCs and OHCs may be entirely absent in severely affected regions of the cochlear duct
  (MGI Ref ID J:48863)

• increased Purkinje cell number
  • the numerical density of Purkinje cells is slightly increased
  (MGI Ref ID J:48863)

• abnormal cerebellar granule cell morphology
  • the numerical density of granule cells is decreased while the percentage of pyknotic granule cells is increased
  (MGI Ref ID J:48863)

• abnormal cerebral cortex morphology
  (MGI Ref ID J:108937)

• abnormal cochlear nerve morphology
  • in some regions of the cochlear duct, myelinated nerve fibers, and Schwann cells fill Rosenthal's canals but are reduced in number or absent in others
  (MGI Ref ID J:48863)

growth/size/body region phenotype

• decreased body weight
  • homozygotes exhibit a ~20-30% reduction in body weight relative to wild-type or heterozygous mice
  (MGI Ref ID J:48863)