Phenotypes Associated with This Genotype

Genotype
MGI:2682644

• Allelic Composition: Slc4a7^tm1Krtz/Slc4a7^tm1Krtz
• Genetic Background: involves: 129S5/SvEvBrd * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

hearing/vestibular/ear

collapsed Reissner membrane ( J:86635 )

• at 1 month, homozygotes exhibit a collapsed Reissner membrane

cochlear hair cell degeneration ( J:86635 , J:102942 )

• homozygotes display progressive cochlear hair cell degeneration (J:102942)

• in contrast, hair cells and supporting cells in the vestibular periphery as well as cells within the crista and utricle stroma remain normal from P2 tp P90 (J:102942)

cochlear inner hair cell degeneration ( J:86635 , J:102942 )

• at 1 month, homozygotes exhibit progressive IHC degeneration that becomes severe by 3 months (J:86635)

• at P21, homozygotes display IHC degeneration in the basal cochlear region, not evident at P15 (J:102942)

• by P30 and P90, homozygotes show complete loss of IHCs in the hook region (J:102942)

cochlear outer hair cell degeneration ( J:86635 , J:102942 )

• at 1 month, homozygotes exhibit progressive OHC degeneration that becomes severe by 3 months (J:86635)

• at P21, homozygotes display OHC degeneration in the basal cochlear region, not evident at P15 (J:102942)

• by P30 and P90, homozygotes show complete loss of OHCs in the hook region (J:102942)

abnormal Claudius cell morphology ( J:102942 )

• at P21, Claudius cells appear damaged

degeneration of organ of Corti supporting cells ( J:102942 )

• at P21, homozygotes display degeneration of supporting cells in the basal cochlear region, not evident at P15

• by P30, homozygotes show a marked loss of supporting cells in the organ of Corti

abnormal spiral ligament morphology ( J:86635 )

• at 1 month, homozygotes display morphological changes in the spiral ligament

abnormal spiral ligament fibrocyte morphology ( J:102942 )

• starting at P21, homozygotes show a progressive loss of type II and IV spiral ligament fibrocytes in the basal to hook regions of the cochlea

• however, no fibrocyte loss is noted in the mid-apical cochlear region at all stages

• notably, type III fibrocytes appear morphologically normal at P30 and P90

abnormal type I spiral ligament fibrocytes ( J:102942 )

• at P30 and P90, type I fibrocytes display clear spaces in the extracellular matrix

type II spiral ligament fibrocyte degeneration ( J:102942 )

• at P30 and P90, homozygotes show a significant loss of type II fibrocytes in the basal to hook regions; less pronounced at P21

• at P30 and P90, type II fibrocytes show cytoplasmic vacuolization and a certain degree of cellular shrinkage

type IV spiral ligament fibrocyte degeneration ( J:102942 )

• at P30 and P90, homozygotes show a significant loss of type IV fibrocytes in the basal to hook regions; less pronounced at P21

• at P30 and P90, type IV fibrocytes exhibit cellular shrinkage

abnormal stria vascularis morphology ( J:86635 )

• at 1 month, homozygotes display morphological changes in the stria vascularis

cochlear degeneration ( J:86635 )

• at 1 month, homozygotes show degenerative changes in the basal cochlear region while the mid and apical regions appear unaffected

organ of Corti degeneration ( J:102942 )

• at P15, homozygotes show a mild degeneration of the organ of Corti in the basal cochlear region; not evident at P8

• at P21, the organ of Corti is atrophic in the hook region; however, midbasal to apical cochlear region, stria vascularis, Reissner's membrane and spiral ligament remain normal

abnormal auditory brainstem response waveform shape ( J:86635 )

• by 3 months, homozygotes show significantly lower ABR amplitudes relative to wild-type mice

increased or absent threshold for auditory brainstem response ( J:86635 )

• homozygotes exhibit increased ABR thresholds above 2 kHz; a threshold difference of 20 dB is detected at 32 kHz, indicating a mild auditory impairment

• however, no major vestibular or motor abnormalities are noted at 1-12 months of age during rotarod and tilt-table expts

vision/eye

abnormal retina apoptosis ( J:86635 )

• at 2.5 months, homozygotes exhibit apoptotic nuclei in retinal photoreceptors

abnormal ocular fundus morphology ( J:86635 )

• at 4 months, homozygotes exhibit abnormal fundus morphology, with blood vessel attenuation and diffuse granularity as observed in retinitis pigmentosa; not evident at 1 month of age

abnormal retina vasculature morphology ( J:86635 )

• at 4 months, homozygotes exhibit blood vessel attenuation in the fundus

decreased retina photoreceptor cell number ( J:86635 )

• at 2 months, homozygotes contain a reduced number of photoreceptor cell nuclei in the outer nuclear layer (ONL); the inner retina remains unaffected

• by 11 months, the superior retina is almost devoid of photoreceptor cells

• only a few scattered nuclei are detected at 14 months

short photoreceptor outer segment ( J:86635 )

• at 2 months, homozygotes display shorter photoreceptor outer segments

photoreceptor outer segment degeneration ( J:86635 )

• by 11 months, photoreceptor outer segments are lost and nerve cell process of inner retinal neurons abut the tips of RPE microvilli

retina photoreceptor degeneration ( J:86635 )

• homozygotes exhibit slow photoreceptor death that is nearly complete by 1 year of age

thin retina outer nuclear layer ( J:86635 )

• at 2 months, homozygotes display a ~25% reduction in ONL thickness

• at 6 months, homozygotes show a ~75% reduction in superior ONL thickness and a ~60% reduction in inferior ONL thickness

• at 14 months, the inferior retina is only ~35% of wild-type thickness

abnormal rod electrophysiology ( J:86635 )

• rod-mediated ERGs indicate loss of V_max (the maximum saturated b-wave amplitude) and an elevation of k (the semi-saturation intensity) with increasing age

• by ~12 months, the V_max amplitude is less than 10% of the value noted at 1 month while k is more than doubled

• however, at 2.5 months, rod sensitivity to light is unaffected in surviving photoreceptors, suggesting that Ca²⁺ homeostasis in the outer segment is normal

blindness ( J:86635 )

• homozygotes are viable and fertile with no significant changes in development, behavior, kidney and epididymis morphology and serum or urine electrolyte composition

• however, homozygotes develop blindness due to progressive degeneration of retinal photoreceptors

nervous system

cochlear hair cell degeneration ( J:86635 , J:102942 )

• homozygotes display progressive cochlear hair cell degeneration (J:102942)

• in contrast, hair cells and supporting cells in the vestibular periphery as well as cells within the crista and utricle stroma remain normal from P2 tp P90 (J:102942)

cochlear inner hair cell degeneration ( J:86635 , J:102942 )

• at 1 month, homozygotes exhibit progressive IHC degeneration that becomes severe by 3 months (J:86635)

• at P21, homozygotes display IHC degeneration in the basal cochlear region, not evident at P15 (J:102942)

• by P30 and P90, homozygotes show complete loss of IHCs in the hook region (J:102942)

cochlear outer hair cell degeneration ( J:86635 , J:102942 )

• at 1 month, homozygotes exhibit progressive OHC degeneration that becomes severe by 3 months (J:86635)

• at P21, homozygotes display OHC degeneration in the basal cochlear region, not evident at P15 (J:102942)

• by P30 and P90, homozygotes show complete loss of OHCs in the hook region (J:102942)

decreased retina photoreceptor cell number ( J:86635 )

• at 2 months, homozygotes contain a reduced number of photoreceptor cell nuclei in the outer nuclear layer (ONL); the inner retina remains unaffected

• by 11 months, the superior retina is almost devoid of photoreceptor cells

• only a few scattered nuclei are detected at 14 months

short photoreceptor outer segment ( J:86635 )

• at 2 months, homozygotes display shorter photoreceptor outer segments

photoreceptor outer segment degeneration ( J:86635 )

• by 11 months, photoreceptor outer segments are lost and nerve cell process of inner retinal neurons abut the tips of RPE microvilli

retina photoreceptor degeneration ( J:86635 )

• homozygotes exhibit slow photoreceptor death that is nearly complete by 1 year of age

cochlear ganglion degeneration ( J:86635 , J:102942 )

• by 3 months, homozygotes display a moderate loss of spiral ganglion neurons (J:86635)

• by P30 and P90, homozygotes show complete loss of spiral ganglion neurons in the hook region (J:102942)

• degeneration of myelin surrounding the spiral ganglion neurons is noted at P30 and P90 (J:102942)

• cytoplasmic vacuolation of spiral gnaglian neurons is noted at P90 (J:102942)

• in contrast, vestibular ganglion neurons and their fibers remain normal at all stages (J:102942)

cardiovascular system

abnormal retina vasculature morphology ( J:86635 )

• at 4 months, homozygotes exhibit blood vessel attenuation in the fundus

skeleton

abnormal spiral ligament morphology ( J:86635 )

• at 1 month, homozygotes display morphological changes in the spiral ligament

abnormal spiral ligament fibrocyte morphology ( J:102942 )

• starting at P21, homozygotes show a progressive loss of type II and IV spiral ligament fibrocytes in the basal to hook regions of the cochlea

• however, no fibrocyte loss is noted in the mid-apical cochlear region at all stages

• notably, type III fibrocytes appear morphologically normal at P30 and P90

abnormal type I spiral ligament fibrocytes ( J:102942 )

• at P30 and P90, type I fibrocytes display clear spaces in the extracellular matrix

type II spiral ligament fibrocyte degeneration ( J:102942 )

• at P30 and P90, homozygotes show a significant loss of type II fibrocytes in the basal to hook regions; less pronounced at P21

• at P30 and P90, type II fibrocytes show cytoplasmic vacuolization and a certain degree of cellular shrinkage

type IV spiral ligament fibrocyte degeneration ( J:102942 )

• at P30 and P90, homozygotes show a significant loss of type IV fibrocytes in the basal to hook regions; less pronounced at P21

• at P30 and P90, type IV fibrocytes exhibit cellular shrinkage

cellular

abnormal retina apoptosis ( J:86635 )

• at 2.5 months, homozygotes exhibit apoptotic nuclei in retinal photoreceptors

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Usher syndrome type 2C		DOID:0110839	OMIM:605472	J:86635