Overview

Also Known As:deaf5

This ENU induced mutation results in the absence otoferlin and profound deafness, but no impact on vestibular-evoked potentials.

Genetic overview

Genetic Background	Generation

Otof^deaf5Jcs

Allele Type	Gene Symbol	Gene Name
Chemically induced (ENU)	Otof	otoferlin

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Research Applications

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Base Price

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$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Expression of the otoferlin gene is not detected in these mutant mice, indicating that this missense mutation has a severe effect on the stability of the protein and potentially its localization. Auditory brainstem response analysis demonstrated that mice homozygous for the missense mutation are profoundly deaf, consistent with an essential role for otoferlin in inner hair cell neurotransmission. Vestibular-evoked potentials of mutant mice, however, is equivalent to those of wildtype mice, indicating that otoferlin is unnecessary for vestibular function even though it is highly expressed in both vestibular and cochlear hair cells.

Wright et al. found multiple reasons for failed neurotransmission from hair cells, despite normal tonotopic organization. The volume of the ventral cochlear nuclei is smaller than normal by nearly half, the auditory nerve is approximately half the normal thickness, the end bulbs of Held are fewer in number, wispier, and less branched than normal, and some of the axons leading to them are thinner. The bushy cells are contacted by slightly more nerve fibers in mutants (average 2.6) then in hearing controls (average 2.0) and the spontaneous miniature excitatory postsynaptic currents are 24% larger in mutants, despite occurring with similar frequencies and with similar shapes to those of hearing controls.

Development

The deaf5Jcs mutation was generated by ENU mutagenesis of C57BL/6J males, which were then bred with C3HeB/FeJ-Rw/+ females to permit tracking of the mutated male-derived Chromosome 5. The male G1 offspring of this cross were then bred with Rw +/+ Hm females and the non-Hm-bearing Rw/+ offspring, which would carry the Chromosome 5 that was potentially mutagenized in the Rw deletion region, were selected and intercrossed to reveal any recessive mutations. Clickbox screening revealed the deaf5Jcs mutation. A homozygous deaf5Jcs male, on this mixed background of predominantly C57BL/6J and C3HeB/FeJ, was bred to a BALB/cJ female and the resulting offspring were intercrossed. A homozygous male from this STOCK background was sent from Dr. John Schimenti at Cornell University to Dr. Kenneth Johnson at The Jackson Laboratory, and in vitro fertilization was carried out with C3HeB/FeJ females. The line was then sibling inbred and reached generation F5 in 2007.

Control Suggestions

Heterozygote from the colony

Additional Information

Considerations for Choosing Controls

Selected References

Longo-Guess C; Gagnon LH; Bergstrom DE; Johnson KR. 2007. A missense mutation in the conserved C2B domain of otoferlin causes deafness in a new mouse model of DFNB9 Hear Res 234(1-2):21-8PubMed: 17967520 MGI: J:125960
Wilson L; Ching YH; Farias M; Hartford SA; Howell G; Shao H; Bucan M; Schimenti JC. 2005. Random mutagenesis of proximal mouse chromosome 5 uncovers predominantly embryonic lethal mutations. Genome Res 15(8):1095-105PubMed: 16024820 MGI: J:100332
Wright S; Hwang Y; Oertel D. 2014. Synaptic transmission between end bulbs of Held and bushy cells in the cochlear nucleus of mice with a mutation in Otoferlin. J Neurophysiol 112(12):3173-88PubMed: 25253474 MGI: J:269136

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Genetics

Otof^deaf5Jcs

Allele Symbol: Otof^deaf5Jcs

Allele Name	deaf 5, John C Schimenti
Allele Type	Chemically induced (ENU)
Allele Synonym(s)
Gene Symbol and Name	Otof, otoferlin
Gene Synonym(s)
Strain of Origin	C57BL/6J
Chromosome	5
Molecular Note	A T to A base substitution in exon 10 yields an isoleucine to asparagine change in a highly conserved residue of the C2B protein domain and immunohistochemistry of the cochlea fails to detect this protein.

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

autosomal recessive nonsyndromic deafness 9

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Otof^deaf5Jcs/Otof^deaf5Jcs
STOCK Otof/Kjn

behavior/neurological phenotype

absent pinna reflex

hearing/vestibular/ear phenotype

abnormal hearing electrophysiology
- bushy cells from homozygotes fire action potentials to less steeply rising depolarizations than in unaffected controls, miniature excitatory postsynaptic currents are larger and carry more charge than in unaffected controls

deafness

increased or absent threshold for auditory brainstem response
- ABR could not be detected in homozygotes at 4 weeks of age

mammalian phenotype

hearing/vestibular/ear phenotype
- vestibular-evoked potential is normal and movement, righting responses, and swim tests are normal indicating normal vestibular function

nervous system phenotype

abnormal cochlear nerve morphology
- the auditory nerve is reduced by an average of 54%, the end bulbs of Held and the axons to them are smaller than normal, there are fewer end bulbs and they are thinner and more wispy with fewer branches per end than normal

abnormal paired-pulse facilitation

abnormal synaptic transmission
- distortion product acoustic emissions are normal, but auditory brainstem responses are not, consistent with failed synaptic transmission between cochlear hair cells and spiral ganglion cells

decreased cochlear VIII nucleus size
- the ventral cochlear nuclei are significantly smaller than normal, volumes reduced by 46%, and that of the dorsal cochlear nuclei did not reach significance

Genotype: Otof^deaf5Jcs/Otof⁺
STOCK Otof/Kjn

mammalian phenotype

hearing/vestibular/ear phenotype
- heterozygotes display normal ABR thresholds

References

Longo-Guess C; Gagnon LH; Bergstrom DE; Johnson KR. 2007. A missense mutation in the conserved C2B domain of otoferlin causes deafness in a new mouse model of DFNB9 Hear Res 234(1-2):21-8PubMed: 17967520 MGI: J:125960
Wilson L; Ching YH; Farias M; Hartford SA; Howell G; Shao H; Bucan M; Schimenti JC. 2005. Random mutagenesis of proximal mouse chromosome 5 uncovers predominantly embryonic lethal mutations. Genome Res 15(8):1095-105PubMed: 16024820 MGI: J:100332
Wright S; Hwang Y; Oertel D. 2014. Synaptic transmission between end bulbs of Held and bushy cells in the cochlear nucleus of mice with a mutation in Otoferlin. J Neurophysiol 112(12):3173-88PubMed: 25253474 MGI: J:269136

Additional - Otof^deaf5Jcs related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Sanger sequencing:Otof
- End Point Analysis:Otof EP
- Genotyping resources and troubleshooting
Citation
When using the deaf5 mouse strain in a publication, please cite the originating article(s) and include JAX stock #006128 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or wildtype for Otof<deaf5Jcs>

Related Products and Services

Frozen Mouse Embryo	STOCK Otof<deaf5Jcs>/Kjn Frozen Embryos	$2595.00
Frozen Mouse Embryo	STOCK Otof<deaf5Jcs>/Kjn Frozen Embryos	$2595.00
Frozen Mouse Embryo	STOCK Otof<deaf5Jcs>/Kjn Frozen Embryos	$3373.50
Frozen Mouse Embryo	STOCK Otof<deaf5Jcs>/Kjn Frozen Embryos	$3373.50

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Also Known As:deaf5

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Otofdeaf5Jcs

Allele Symbol: Otofdeaf5Jcs

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Otofdeaf5Jcs/Otofdeaf5JcsSTOCK Otof/Kjn

behavior/neurological phenotype

hearing/vestibular/ear phenotype

mammalian phenotype

nervous system phenotype

Genotype: Otofdeaf5Jcs/Otof+STOCK Otof/Kjn

mammalian phenotype

References

Additional - Otofdeaf5Jcs related

Genotyping Protocols

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Otof^deaf5Jcs

Allele Symbol: Otof^deaf5Jcs

Genotype: Otof^deaf5Jcs/Otof^deaf5Jcs
STOCK Otof/Kjn

Genotype: Otof^deaf5Jcs/Otof⁺
STOCK Otof/Kjn

Additional - Otof^deaf5Jcs related