Phenotypes for Slc26a4 MGI:3697081 MGI Mouse

distended Reissner membrane ( J:101834 )

• large bulging of Reissner's membrane

dilated cochlea ( J:116301 )

• adult homozygotes exhibit a dilated cochlea, despite normal postnatal cochlear development and the presence of a well-formed tunnel of Corti

cochlear hair cell degeneration ( J:101834 )

organ of Corti degeneration ( J:101834 , J:116301 )

• at ~6 weeks, homozygotes display severe degeneration of the organ of Corti (J:116301)

type I spiral ligament fibrocyte degeneration ( J:101834 )

• apparent loss of type I fibrocytes

type II spiral ligament fibrocyte degeneration ( J:101834 )

• apparent loss of type II fibrocytes

thin spiral ligament ( J:101834 , J:116301 )

• spiral prominence is less prominent and spiral ligament is thinner than normal (J:101834)

• at ~6 weeks, homozygotes show a severe reduction of the spiral ligament in the lateral wall of the cochlea (J:116301)

abnormal strial basal cell morphology ( J:101834 , J:116301 )

• however, basal cells at the top and bottom of stria vascularis form tight junctions with surface epithelial cells (J:101834)

• at ~P30, presence of round and oval-shaped openings suggest degeneration of the strial basal cell layer and possible destruction of the basal tight junctional barrier (J:116301)

abnormal strial intermediate cell morphology ( J:101834 , J:116301 )

• between P7 and P15, intermediate cells are present in stria vascularis, but appear hyperpigmented (J:101834)

• at ~P30, homozygotes show signs of degeneration in strial intermediate cells (J:116301)

abnormal strial marginal cell morphology ( J:101834 , J:116301 )

• marginal cells appear to form a continuous layer, with an aberrant pattern of tight junctions (J:101834)

• at ~P30, marginal cells fail to exhibit a typical cobblestone pattern and show aberrant shapes and sizes (J:116301)

stria vascularis degeneration ( J:101834 , J:116301 )

• degeneration of stria vascularis, as evidenced by hyperpigmentation (suggesting unalleviated free radical damage) and an irregular pattern of tight junctions in marginal cells (J:101834)

• at ~P30, homozygotes display signs of stria vascularis degeneration (J:116301)

thin stria vascularis ( J:116301 )

• at ~6 weeks, homozygotes display a significantly thinned stria vascularis (~2/3 of wild-type thickness)

dilated scala media ( J:101834 )

• enlargement of the scala media

small scala tympani ( J:116301 )

• at ~6 weeks, homozygotes typically exhibit a significantly smaller scala tympani

abnormal spiral limbus morphology ( J:101834 )

• spiral limbus appears flatter than normal

dilated endolymphatic duct ( J:116301 )

• at ~6 weeks, homozygotes show an increased volume of endolymphatic spaces (i.e. severe endolymphatic hydrops)

enlarged otoliths ( J:101834 , J:121448 )

• homozygotes are identified by the presence of one or few very large rhomboedric otoconia in utricular macula (J:101834)

• at P30-P142, homozygotes display a single giant crystal, presumably CaCO₃, instead of normal otoconia in the utricle (J:121448)

abnormal cochlear endolymph ionic homeostasis ( J:121442 )

• at all ages (i.e. both before and after the onset of hearing), the endolymphatic pH of homozygotes is more acidic than the perilymphatic pH

• no difference in the pH of perilymph or blood between wild-type and homozygous mutant mice is observed

• in contrast to heterozygotes, endolymphatic Ca²⁺ concentration in homozygotes is similar to perilymphatic Ca²⁺ concentration at P10 and progressively increases during further development

• no difference in the Ca²⁺ concentration of perilymph or blood between wild-type and homozygous mutant mice is observed

absent endocochlear potential ( J:101834 , J:116301 )

• no significant differences in perilymphatic or plasma K⁺ concentrations are observed (J:101834)

• loss of endocochlear potential is associated with absence of the KCNJ10 K⁺ channel in stria vascularis but not in spiral ganglia (J:101834)

• expression of KCNJ10 mRNA is normal in stria vascularis and spiral ganglia of young homozygotes (1-4 months) but significantly reduced in older homozygotes (~12 months) (J:101834)

• at ~6 weeks, homozygotes show near absence of a normal EP in both the basal and apical cochlear turns (J:116301)

• induction of anoxia results in a reduced magnitude of the negative EP value, consistent with a loss of functional hair cells (J:116301)

• notably, cochlear endolymphatic [K⁺], as well as utricular potential (UP) and utricular endolymphatic [K⁺] remain normal (J:116301)

decreased endocochlear potential ( J:121442 )

• at P10, homozygotes generate a small endocochlear potential which is progressively lost during further development

• consistent with this finding, protein expression of K⁺ channel Kcnj10 in the stria vascularis is noted at P10 but is progressively lost during further development

abnormal vestibular endolymph physiology ( J:121448 )

• young adult homozygotes (P30-P142) display a small, but statistically significant, reduction of ~3 mV in utricular endolymphatic potential (UP) relative to wild-type mice

abnormal vestibular endolymph ionic homeostasis ( J:121448 )

• at P30-P142, homozygotes display a significantly lower pH and higher [Ca²⁺] in utricular endolymph relative to wild-type or heterozygous mice

• in addition, utricular endolymphatic [Ca²⁺] is significantly increased to a level higher than in perilymph, consistent with the presence of altered otoconia

• however, no significant differences are observed in perilymphatic pH and [Ca²⁺] relative to control values

increased or absent threshold for auditory brainstem response ( J:121442 )

• homozygotes lack hearing at all ages tested, as determined by auditory brain stem recordings using click and tone-burst stimuli at 8, 16, and 32 kHz

deafness ( J:121442 )

• homozygotes fail to develop hearing

nonsyndromic hearing loss ( J:67072 )

• at least on a 129Sv/Ev background, homozygotes display non-syndromic deafness with no evidence of thyroid disease

sensorineural hearing loss ( J:116301 )

abnormal strial intermediate cell morphology ( J:101834 , J:116301 )

• between P7 and P15, intermediate cells are present in stria vascularis, but appear hyperpigmented (J:101834)

• at ~P30, homozygotes show signs of degeneration in strial intermediate cells (J:116301)

endocrine/exocrine gland phenotype ( J:67072 , J:139883 )

N	• at least a 129Sv/Ev background, homozygotes exhibit no signs of overt hypothyroidism at any age up to 2 years; standard serum thyroid function tests are normal (J:67072) • thyroid morphology and function are normal (J:139883)

cochlear hair cell degeneration ( J:101834 )

abnormal calcium ion homeostasis ( J:121442 , J:121448 )

• endolymphatic acidification causes inhibition of Ca²⁺ reabsorption from the vestibular endolymph via the acid-sensitive Ca²⁺ channels Trpv5 and Trpv6; as a result, the endolymphatic Ca2⁺ concentration is progressively increased (J:121442)

• vestibular dysfunction is partly attributed to a pathological elevation of utricular endolymphatic [Ca²⁺] due to luminal acidification and consequent inhibition of TRPV5/6-mediated Ca²⁺ absorption (J:121448)

head tilt ( J:121448 )

circling ( J:121448 )