Phenotypes associated with this allele

• Allele Symbol: Pou4f3^tm1Rsd
• Allele Name: targeted mutation 1, Michael G Rosenfeld
• Allele ID: MGI:2176270
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Pou4f3^tm1Rsd/Pou4f3^tm1Rsd	involves: 129S4/SvJae	MGI:3583887
hm2	Pou4f3^tm1Rsd/Pou4f3^tm1Rsd	involves: 129S4/SvJae * C57BL/6	MGI:3688922
ht3	Pou4f3^tm1Rsd/Pou4f3^+	involves: 129S4/SvJae * C57BL/6	MGI:3688923

Genotype
MGI:3583887

hm1

• Allelic Composition: Pou4f3^tm1Rsd/Pou4f3^tm1Rsd
• Genetic Background: involves: 129S4/SvJae

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

behavior/neurological

abnormal motor coordination/balance ( J:33502 )

• severe deficits in balance and coordination by P14

hyperactivity ( J:33502 )

• marked hyperactivity by 5-6 weeks

hearing/vestibular/ear

abnormal cochlea morphology ( J:207266 )

• 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

abnormal cochlear sensory epithelium morphology ( J:207266 )

• 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

abnormal organ of Corti morphology ( J:33502 )

• incomplete cavitation of the organ of Corti at P0

abnormal cochlear hair cell development ( J:33502 )

• at P0, IHCs and OHCs in the organ of Corti fail to show early signs of differentiation

absent cochlear hair cells ( J:33502 , J:207266 )

• by P14, no hair cells are identified in the organ of Corti (J:33502)

• auditory epithelium contains no sensory hair cells (J:207266)

absent cochlear hair cell stereocilia ( J:33502 , J:207266 )

• lack of stereocilia in the auditory epithelium (J:207266)

abnormal cochlear inner hair cell morphology ( J:33502 )

• 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

absent inner hair cell stereocilia ( J:33502 )

abnormal cochlear outer hair cell morphology ( J:33502 )

• 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

absent outer hair cell stereocilia ( J:33502 )

abnormal cuticular plate morphology ( J:207266 )

• lack of cuticular plate in the auditory epithelium

absent organ of Corti supporting cells ( J:33502 )

• by P14, many of the normal supporting cell populations are absent in the organ of Corti

absent tunnel of Corti ( J:207266 )

• tunnel of Corti is sometimes absent

absent vestibular hair cells ( J:33502 )

• 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

absent vestibular hair cell stereocilia ( J:33502 )

• at P0, stereocilia bundles are absent in the sensory epithelia of the maculae and the cristae

increased or absent threshold for auditory brainstem response ( J:33502 )

• at P42, mice exhibit a complete failure of click-evoked ABRs to stimuli up to 80 dB above normal threshold

deafness ( J:33502 )

• complete deafness by P42

nervous system

abnormal cochlear hair cell development ( J:33502 )

• at P0, IHCs and OHCs in the organ of Corti fail to show early signs of differentiation

absent cochlear hair cells ( J:33502 , J:207266 )

• by P14, no hair cells are identified in the organ of Corti (J:33502)

• auditory epithelium contains no sensory hair cells (J:207266)

absent cochlear hair cell stereocilia ( J:33502 , J:207266 )

• lack of stereocilia in the auditory epithelium (J:207266)

abnormal cochlear inner hair cell morphology ( J:33502 )

• 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

absent inner hair cell stereocilia ( J:33502 )

abnormal cochlear outer hair cell morphology ( J:33502 )

• 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

absent outer hair cell stereocilia ( J:33502 )

absent vestibular hair cells ( J:33502 )

• 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

absent vestibular hair cell stereocilia ( J:33502 )

• at P0, stereocilia bundles are absent in the sensory epithelia of the maculae and the cristae

abnormal vestibulocochlear ganglion morphology ( J:207266 )

• 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

cochlear ganglion degeneration ( J:33502 )

• at P0, the cochlea and spiral ganglion appear grossly normal

• however, most spiral ganglion cells degenerate by P14

vestibular ganglion degeneration ( J:33502 )

• complete degeneration of vestibular ganglion by P14, with absence of calycial endings surrounding type I hair cells

Genotype
MGI:3688922

hm2

• Allelic Composition: Pou4f3^tm1Rsd/Pou4f3^tm1Rsd
• Genetic Background: involves: 129S4/SvJae * C57BL/6

behavior/neurological

hyperactivity ( J:57149 )

• at 1 month of age, homozygotes display hyperactivity

circling ( J:57149 )

• at 1 month of age, homozygotes tend to circle

hearing/vestibular/ear

abnormal cochlea morphology ( J:57149 )

abnormal organ of Corti supporting cell differentiation ( J:57149 )

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

small Rosenthal canal ( J:57149 )

• 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

abnormal basilar membrane morphology ( J:57149 )

• 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

absent cochlear hair cells ( J:57149 )

• 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

degeneration of organ of Corti supporting cells ( J:57149 )

• by 18 months, supporting cells show complete degeneration in some areas

organ of Corti degeneration ( J:57149 )

• at 18 months, homozygotes display severe degeneration of the organ of Corti

stria vascularis degeneration ( J:57149 )

• at 18 months, the stria vascularis is normal except in the extreme apex where it is thin and degenerated

deafness ( J:57149 )

• at 5-7 weeks of age, homozygotes are deaf

nervous system

absent cochlear hair cells ( J:57149 )

• 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

abnormal cochlear ganglion morphology ( J:57149 )

• at 18 months, the spiral ganglion consists of a few neurons and myelinated fibers although these lack hair cell targets

cochlear ganglion degeneration ( J:57149 )

• 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

abnormal autonomic nervous system physiology ( J:81013 )

• 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

abnormal body temperature homeostasis ( J:81013 )

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

abnormal circadian temperature homeostasis ( J:81013 )

• in response to hypergravity (2G), homozygotes fail to exhibit the expected reduction in circadian rhythm amplitude which normally lasts for ~7 days

cellular

abnormal organ of Corti supporting cell differentiation ( J:57149 )

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

Genotype
MGI:3688923

ht3

• Allelic Composition: Pou4f3^tm1Rsd/Pou4f3⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6

hearing/vestibular/ear

hearing/vestibular/ear phenotype ( J:57149 )

N • at 2, 18 and 24 months of age, heterozygotes exhibit a comparable hearing to wild-type mice, with similar patterns of cochlear degeneration

N • 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		DO ID	OMIM ID(s)	Ref(s)
NOT	autosomal dominant nonsyndromic deafness 15	DOID:0110546	OMIM:602459	J:57149