Phenotypes associated with this allele

• Allele Symbol: Atoh1^tm2Hzo
• Allele Name: targeted mutation 2, Huda Y Zoghbi
• Allele ID: MGI:2155983
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Atoh1^tm2Hzo/Atoh1^tm2Hzo	Not Specified	MGI:2183424
ht2	Atoh1^tm2Hzo/Atoh1^tm3.1Hzo	involves: 129S7/SvEvBrd * C57BL/6J * FVB/N * SJL	MGI:3767182
cn3	Atoh1^tm2Hzo/Atoh1^tm3Hzo Tg(Fabp1-cre)1Jig/0	involves: 129S7/SvEvBrd * C57BL/6J * FVB/N * SJL	MGI:3767181
cn4	Atoh1^tm2Hzo/Atoh1^tm3Hzo Tg(Vil1-cre)997Gum/0	involves: 129S7/SvEvBrd * C57BL/6J * SJL	MGI:3767180
cx5	Atoh1^tm2Hzo/Atoh1^+ Tcf4^tm1Zhu/Tcf4^+	involves: 129P2/OlaHsd	MGI:3776856
cx6	Atoh1^tm2Hzo/Atoh1^+ Gfi1^tm1Sho/Gfi1^tm1Sho	involves: 129S1/Sv * C57BL/6J	MGI:3696821

Genotype
MGI:2183424

hm1

• Allelic Composition: Atoh1^tm2Hzo/Atoh1^tm2Hzo
• Genetic Background: Not Specified

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

mortality/aging

neonatal lethality, complete penetrance ( J:60393 , J:155760 )

• animals die shortly after birth (J:60393)

• reported to make occasional gasps after birth (J:155760)

• unresponsive by 30-45 minutes after birth (J:155760)

hearing/vestibular/ear

absent cochlear hair cells ( J:55694 )

absent vestibular hair cells ( J:55694 )

• hair cells were absent from utricles and cochlea

homeostasis/metabolism

cyanosis ( J:60393 )

respiratory system

decreased pulmonary respiratory rate ( J:155760 )

• diaphragmatic electromyograms indicate slow and variable respiratory rhythms involving the phrenic nerve

• rhythms also slow when recorded from hypoglossal and C4 nerves when the diaphragm is not part of the experimental preparation

• glutamatergic modulators such as dihydrokainic acid and ampakine (CX546) restore near normal rhythm and pattern in expermimental preparations

• substance P increases respiratory rhythm but does not restore normal frequency or pattern

• norepinephrin establishes a similar slow, regular pace in both mutant and control experimental preparations

respiratory failure ( J:60393 )

• animals do not breathe after birth

nervous system

nervous system phenotype ( J:60393 )

N • normal hindbrain: normal nucleus tractus solitarus, nucleus ambiguus, dorsal vagus nucleus and trigeminal ganglion

absent cochlear hair cells ( J:55694 )

absent vestibular hair cells ( J:55694 )

• hair cells were absent from utricles and cochlea

abnormal hindbrain development ( J:105186 )

• in null embryos, certain nuclei of the rostrolateral region of the hindbrain that originate in the cerebellar rhombic lip fail to form; nuclei such as the pontine nuclei and the external granule layer do not seem to form in the rostrolateral hindbrain but are present at more caudal positions in mutant brains

absent cerebellar foliation ( J:60393 )

abnormal cerebellum external granule cell layer morphology ( J:60393 )

• absent external granule layer: migrating granule cells absent as early as E14 in rhombic lip

abnormal cerebellar Purkinje cell layer ( J:60393 )

• disorganized and cells localized at periphery of cerebellum

small cerebellum ( J:60393 )

Genotype
MGI:3767182

ht2

• Allelic Composition: Atoh1^tm2Hzo/Atoh1^tm3.1Hzo
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J * FVB/N * SJL

mortality/aging

neonatal lethality, complete penetrance ( J:128312 )

• die at birth and are stated to be phenotypically indistinguishable from Atoh1^tm2Hzo homozygous mice

Genotype
MGI:3767181

cn3

• Allelic Composition: Atoh1^tm2Hzo/Atoh1^tm3Hzo; Tg(Fabp1-cre)1Jig/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J * FVB/N * SJL

mortality/aging

mortality/aging ( J:128312 )

N • unlike mice with complete recombination of the floxed allele in the entire intestinal epithelium, mice with a mosaic pattern of recombination show no increase in mortality up to at least 1 year of age

digestive/alimentary system

abnormal small intestine crypts of Lieberkuhn morphology ( J:128312 )

• the small intestine contains patches of abnormal crypts with a recombined allele mixed with areas of normal crypts with an unrecombined allele

• crypts with the recombined allele completely lack goblet, Paneth, and enteroendocrine cells instead containing only absorptive enterocytes

• a significant increase in BrdU+ cells and mitotic figures is seen in crypts with a recombined allele

• crypts with a recombined allele are smaller than neighboring crypts in which recombination did not occur

impaired intestine regeneration ( J:128312 )

• the adaptive response following resection of the middle 50% of the small bowel is blunted with a smaller increase in crypt depth compared to control mice

endocrine/exocrine glands

abnormal small intestine crypts of Lieberkuhn morphology ( J:128312 )

• the small intestine contains patches of abnormal crypts with a recombined allele mixed with areas of normal crypts with an unrecombined allele

• crypts with the recombined allele completely lack goblet, Paneth, and enteroendocrine cells instead containing only absorptive enterocytes

• a significant increase in BrdU+ cells and mitotic figures is seen in crypts with a recombined allele

• crypts with a recombined allele are smaller than neighboring crypts in which recombination did not occur

Genotype
MGI:3767180

cn4

• Allelic Composition: Atoh1^tm2Hzo/Atoh1^tm3Hzo; Tg(Vil1-cre)997Gum/0
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6J * SJL

mortality/aging

postnatal lethality, complete penetrance ( J:128312 )

• no mutants are found at P14

Genotype
MGI:3776856

cx5

• Allelic Composition: Atoh1^tm2Hzo/Atoh1⁺; Tcf4^tm1Zhu/Tcf4⁺
• Genetic Background: involves: 129P2/OlaHsd

nervous system

abnormal neuronal migration ( J:125313 )

• mice die within the first 24 hours of birth but no embryonic lethality is observed as previously noted

abnormal brain development ( J:125313 )

• the pontine nuclei is disrupted

cellular

abnormal neuronal migration ( J:125313 )

• mice die within the first 24 hours of birth but no embryonic lethality is observed as previously noted

Genotype
MGI:3696821

cx6

• Allelic Composition: Atoh1^tm2Hzo/Atoh1⁺; Gfi1^tm1Sho/Gfi1^tm1Sho
• Genetic Background: involves: 129S1/Sv * C57BL/6J

hearing/vestibular/ear

abnormal cochlear hair cell morphology ( J:80025 )

• at E15.5, the characteristic rows of IHCs and OHCs are not as clearly defined in the basal cochlea

• at E17.5, mutants display disorganization of hair cells and decreased hair cell numbers in the basal cochlea

• at P0, the apical cochlea shows little to no hair cell loss, but exhibits a disorganization similar to that seen in basal cochlea at E15.5

cochlear hair cell degeneration ( J:80025 )

• cochlear IHCs and OHCs are initially specified by E15.5 but are subsequently lost in a basal-to-apical gradient at P0

• by P3, the basal cochlea has few hair cells while the medial cochlea still retains most IHCs but has lost almost all OHCs

• in all cases, OHCs in a given region degenerate prior to IHCs cells

abnormal vestibular hair cell morphology ( J:80025 )

• at P0, the saccule shows disorganization of the hair cell layer, with some hair cells found in the supporting cell layer

• in contrast, cristae exhibit a relatively normal development of hair cells

abnormal vestibular hair cell stereociliary bundle morphology ( J:80025 )

• at P0, mutant vestibular hair cells appear to have less well organized stereocillia relative to wild-type hair cells

nervous system

abnormal cochlear hair cell morphology ( J:80025 )

• at E15.5, the characteristic rows of IHCs and OHCs are not as clearly defined in the basal cochlea

• at E17.5, mutants display disorganization of hair cells and decreased hair cell numbers in the basal cochlea

• at P0, the apical cochlea shows little to no hair cell loss, but exhibits a disorganization similar to that seen in basal cochlea at E15.5

cochlear hair cell degeneration ( J:80025 )

• cochlear IHCs and OHCs are initially specified by E15.5 but are subsequently lost in a basal-to-apical gradient at P0

• by P3, the basal cochlea has few hair cells while the medial cochlea still retains most IHCs but has lost almost all OHCs

• in all cases, OHCs in a given region degenerate prior to IHCs cells

abnormal vestibular hair cell morphology ( J:80025 )

• at P0, the saccule shows disorganization of the hair cell layer, with some hair cells found in the supporting cell layer

• in contrast, cristae exhibit a relatively normal development of hair cells

abnormal vestibular hair cell stereociliary bundle morphology ( J:80025 )

• at P0, mutant vestibular hair cells appear to have less well organized stereocillia relative to wild-type hair cells