Mouse Genome Informatics
hm1
    Pou4f3tm1Rsd/Pou4f3tm1Rsd
involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• severe deficits in balance and coordination by P14
• marked hyperactivity by 5-6 weeks

hearing/vestibular/ear
• incomplete cavitation of the organ of Corti at P0
• at P0, IHCs and OHCs in the organ of Corti fail to show early signs of differentiation
• by P14, no hair cells are identified in the organ of Corti
• at P0, IHCs in the organ of Corti fail to show early signs of differentiation, including growth of stereocilia and segregation of cell nuclei to a plane above the level of supporting cell nuclei
• at P0, OHCs in the organ of Corti fail to show early signs of differentiation, including growth of stereocilia and segregation of cell nuclei to a plane above the level of supporting cell nuclei
• by P14, many of the normal supporting cell populations are absent in the organ of Corti
• at P0, no hair cells are identified in the sensory epithelia of the maculae and the cristae; the row of nuclei above the supporting cell nuclei is poorly organized
• at P0, stereocilia bundles are absent in the sensory epithelia of the maculae and the cristae
• at P42, mice exhibit a complete failure of click-evoked ABRs to stimuli up to 80 dB above normal threshold
• complete deafness by P42

nervous system
• at P0, IHCs and OHCs in the organ of Corti fail to show early signs of differentiation
• by P14, no hair cells are identified in the organ of Corti
• at P0, IHCs in the organ of Corti fail to show early signs of differentiation, including growth of stereocilia and segregation of cell nuclei to a plane above the level of supporting cell nuclei
• at P0, OHCs in the organ of Corti fail to show early signs of differentiation, including growth of stereocilia and segregation of cell nuclei to a plane above the level of supporting cell nuclei
• at P0, no hair cells are identified in the sensory epithelia of the maculae and the cristae; the row of nuclei above the supporting cell nuclei is poorly organized
• at P0, stereocilia bundles are absent in the sensory epithelia of the maculae and the cristae
• at P0, the cochlea and spiral ganglion appear grossly normal
• however, most spiral ganglion cells degenerate by P14
• complete degeneration of vestibular ganglion by P14, with absence of calycial endings surrounding type I hair cells


Mouse Genome Informatics
hm2
    Pou4f3tm1Rsd/Pou4f3tm1Rsd
involves: 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• in response to hypergravity (2G), homozygotes fail to exhibit the expected reduction in circadian rhythm amplitude which normally lasts for ~7 days
• at 1 month of age, homozygotes display hyperactivity
• at 1 month of age, homozygotes tend to circle

hearing/vestibular/ear
• at 6 weeks, the organ of Corti contains undifferentiated supporting cells with the exception of some pillar cells
• at 6 weeks, the Rosenthal canal, which contains the spiral ganglion, appears to be smaller than normal
• the channels in the bone in the osseus spiral lamina are also reduced
• at 18 months, the basilar membrane may totally lack cells in the basal turn, while the middle and apical turns contain cells with few organelles
• at 6 weeks, homozygotes display absence of hair cells in the organ of Corti
• however, the tectorial membrane appears to be unaffected by the absence of hair cells or the disruption of the organ of Corti
• by 18 months, supporting cells show complete degeneration in some areas
• at 18 months, homozygotes display severe degeneration of the organ of Corti
• at 18 months, the stria vascularis is normal except in the extreme apex where it is thin and degenerated
• at 5-7 weeks of age, homozygotes are deaf

nervous system
• at 6 weeks, homozygotes display absence of hair cells in the organ of Corti
• however, the tectorial membrane appears to be unaffected by the absence of hair cells or the disruption of the organ of Corti
• at 18 months, the spiral ganglion consists of a few neurons and myelinated fibers although these lack hair cell targets
• at 6 weeks, homozygotes show a significant reduction in the number of spiral ganglion cells in the middle cochlear turn; the basal and apical turns are not as affected
• by 18 months, homozygotes show severe degeneration of the spiral ganglion cells
• in response to hypergravity (2G exposure), homozygotes lack a normal autonomic response i.e. a dramatic drop in body temperature and concomitant circadian adjustment
• however, no differences in mean daily temperature and circadian rhythm amplitude are noted after chronic 2G (2 wks) or during the 1G recovery relative to wild-type littermates
• in addition, unlike wild-type mice, homozygotes show virtually no increase in neuronal activity (i.e. Fos induction) in the vestibular complex and parabrachial nucleus after 2G exposure
• only minor numbers of 2G-induced Fos immunoreactive neurons are detected, mainly in the nucleus of solitary tract (NST) and the central nucleus of amygdala (CNA), suggesting an intact afferent vagal component

homeostasis/metabolism
• in response to hypergravity, homozygotes fail to exhibit the expected dramatic fall in mean body temperature immediately after exposure to 2G

cellular
• at 6 weeks, the organ of Corti contains undifferentiated supporting cells with the exception of some pillar cells


Mouse Genome Informatics
ht3
    Pou4f3tm1Rsd/Pou4f3+
involves: 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hearing/vestibular/ear
N
• at 2, 18 and 24 months of age, heterozygotes exhibit a comparable hearing to wild-type mice, with similar patterns of cochlear degeneration (J:57149)
• both heterozygous and wild-type mice display a ~30 dB hearing loss beginning at 18 months of age, outer hair cell degeneration and loss of spiral ganglion neurons in the basal turn (J:57149)

Mouse Models of Human Disease
OMIM IDRef(s)
NOT Deafness, Autosomal Dominant 15; DFNA15 602459 J:57149