Phenotypes Associated with This Genotype

Genotype
MGI:2671154

• Allelic Composition: Rdx^tm1Sts/Rdx^tm1Sts
• Genetic Background: involves: 129S4/SvJae * C57BL/6

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

Stereocilia abnormalities on Rdx^tm1Sts/Rdx^tm1Sts cochlear hair cells of adult and newborn mice

homeostasis/metabolism

abnormal blood homeostasis ( J:77485 )

increased circulating bilirubin level ( J:77485 )

• serum levels start to rise around 4 weeks of age

• marked conjugated hyperbilirubinemia eventually develops

increased circulating alkaline phosphatase level ( J:77485 )

• serum alkaline phosphatase levels increase after hyperbilirubinemia develops

increased circulating aspartate transaminase level ( J:77485 )

• serum aspartate transaminase levels increase after hyperbilirubinemia develops

liver/biliary system

abnormal liver morphology ( J:77485 )

• liver was normal to 8 weeks of age

• mild degenerative changes were detectable after 16 weeks

• microvilli of the bile canalicular membrane break down

behavior/neurological

absent pinna reflex ( J:124151 )

• at 5-10-weeks of age, homozygotes show absence of Preyer's reflex in response to a loud handclap

• however, adult homozygotes display no signs of imbalance up to P100, consistent with a normal vestibule

• in addition, at 5-10 weeks of age, homozygotes display a normal vestibulo-ocular reflex at all head rotation frequencies

hearing/vestibular/ear

abnormal cochlear hair cell stereociliary bundle morphology ( J:124151 )

• after the onset of hearing, homozygotes display progressive degeneration of ezrin-based stereocilia of cochlear hair cells

• ezrin appears to compensate for radixin deficiency in the development of cochlear hair cell stereocilia, at least up to P14

• in contrast, ezrin-based vestibular stereocilia are maintained normally, with no differences in the number/density or morphology of vestibular stereocilia detected at 5-10 weeks

• no abnormality in otolith organs (utricle and saccule) is observed

abnormal inner hair cell stereociliary bundle morphology ( J:124151 )

• at P40, mutant IHCs display several shorter fused protrusions instead of stereocilia

fused inner hair cell stereocilia ( J:124151 )

short inner hair cell stereocilia ( J:124151 )

abnormal outer hair cell stereociliary bundle morphology ( J:124151 )

• at ~P14, homozygotes begin to exhibit signs of OHC stereocilia degeneration: the central part of the W-shaped row of stereocilia is lost, leaving discontinuous and disorganized arrays of stereocilia

• at 3 weeks, ezrin-based OHC stereocilia are found at various degeneration stages

• during degeneration, ezrin-based OHC stereocilia as well as core bundles appear to be fused to form abnormal thick and short protrusions

• at P40, mutant OHC stereocilia are deformed to 1?3 residual knoblike protrusions on the apical surfaces, instead of being arranged in a ""W"" shape as in wild-type mice

short outer hair cell stereocilia ( J:124151 )

fused outer hair cell stereocilia ( J:124151 )

cochlear hair cell degeneration ( J:124151 )

• at >P90, cochlear hair cells appear to undergo degeneration

• however, no obvious gross morphological malformations are noted in cochlea or hair cells up to P60

organ of Corti degeneration ( J:124151 )

• at >P90, the organ of Corti appears fairly disorganized due to elimination of cochlear hair cells

increased or absent threshold for auditory brainstem response ( J:124151 )

• at 5-10 weeks of age, three homozygotes studied show no auditory-evoked brainstem responses in response to a stimulus with a sound pressure level (SPL) of 70 decibels (dB) at 20 kHz

• at 10 weeks of age, homozygotes exhibit increased ABR thresholds of >70-90 dB SPL relative to wild-type and heterozygous mice which show normal hearing thresholds (10-50 dB SPL)

deafness ( J:124151 )

• at 10 weeks of age, homozygotes are profoundly deaf

nervous system

abnormal cochlear hair cell stereociliary bundle morphology ( J:124151 )

• after the onset of hearing, homozygotes display progressive degeneration of ezrin-based stereocilia of cochlear hair cells

• ezrin appears to compensate for radixin deficiency in the development of cochlear hair cell stereocilia, at least up to P14

• in contrast, ezrin-based vestibular stereocilia are maintained normally, with no differences in the number/density or morphology of vestibular stereocilia detected at 5-10 weeks

• no abnormality in otolith organs (utricle and saccule) is observed

abnormal inner hair cell stereociliary bundle morphology ( J:124151 )

• at P40, mutant IHCs display several shorter fused protrusions instead of stereocilia

fused inner hair cell stereocilia ( J:124151 )

short inner hair cell stereocilia ( J:124151 )

abnormal outer hair cell stereociliary bundle morphology ( J:124151 )

• at ~P14, homozygotes begin to exhibit signs of OHC stereocilia degeneration: the central part of the W-shaped row of stereocilia is lost, leaving discontinuous and disorganized arrays of stereocilia

• at 3 weeks, ezrin-based OHC stereocilia are found at various degeneration stages

• during degeneration, ezrin-based OHC stereocilia as well as core bundles appear to be fused to form abnormal thick and short protrusions

• at P40, mutant OHC stereocilia are deformed to 1?3 residual knoblike protrusions on the apical surfaces, instead of being arranged in a ""W"" shape as in wild-type mice

short outer hair cell stereocilia ( J:124151 )

fused outer hair cell stereocilia ( J:124151 )

cochlear hair cell degeneration ( J:124151 )

• at >P90, cochlear hair cells appear to undergo degeneration

• however, no obvious gross morphological malformations are noted in cochlea or hair cells up to P60

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Dubin-Johnson syndrome		DOID:12308	OMIM:237500	J:77485