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

hearing/vestibular/ear
• loss of neurons and nerve fibers in the apical cochlear turn
• ears have very few fibers in the area of Rosenthal's canal that leads to the osseous spiral lamina
• only a few peripheral nerve fibers are seen, which are thin and appear to preferentially grow toward the actin rich cells but not beyond them
• treatment with an adenovirus expressing BDNF results in robust nerve fiber generation at both the apex and base of the cochlea, showing sprouting of nerve fibers into the epithelium
• sensory epithelium shows no hair cells at 6 weeks of age, and cells with features of Deiters cells, pillar cells, and other supporting cells are not seen, although actin-rich cells are seen; instead, it resembles a flat epithelium, composed of a single layer of cuboidal epithelial cells
• actin-rich cells are clustered in patches along the auditory epithelium
• 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 (J:33502)
• auditory epithelium contains no sensory hair cells (J:207266)
• lack of stereocilia in the auditory epithelium (J:207266)
• 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
• lack of cuticular plate in the auditory epithelium
• by P14, many of the normal supporting cell populations are absent in the organ of Corti
• tunnel of Corti is sometimes absent
• 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 (J:33502)
• auditory epithelium contains no sensory hair cells (J:207266)
• lack of stereocilia in the auditory epithelium (J:207266)
• 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
• the number of spiral ganglion neurons is greatly reduced in Rosenthal's canal
• the spiral ganglion neurons that remain are smaller and outer perimeters are irregular
• treatment with an adenovirus expressing BDNF results in preservation of spiral ganglion neurons
• 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
phenotype observed in males
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
phenotype observed in males
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
• 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

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