Mouse Genome Informatics
hm
    Rdxtm1Sts/Rdxtm1Sts
involves: 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       

Stereocilia abnormalities on Rdxtm1Sts/Rdxtm1Sts cochlear hair cells of adult and newborn mice

homeostasis/metabolism
• serum levels start to rise around 4 weeks of age
• marked conjugated hyperbilirubinemia eventually develops
• serum alkaline phosphatase levels increase after hyperbilirubinemia develops
• serum aspartate transaminase levels increase after hyperbilirubinemia develops

liver/biliary system
• 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
• 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
• 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
• at P40, mutant IHCs display several shorter fused protrusions instead of stereocilia
• 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
• 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
• at >P90, the organ of Corti appears fairly disorganized due to elimination of cochlear hair cells
• 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)
• at 10 weeks of age, homozygotes are profoundly deaf

nervous system
• 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
• at P40, mutant IHCs display several shorter fused protrusions instead of stereocilia
• 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
• 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
OMIM IDRef(s)
Dubin-Johnson Syndrome; DJS 237500 J:77485