Overview

Also Known As:CBA/Ca.129S1(Cg)-Coch^tm1.1Stw/Mmjax

Mice homozygous for this Coch (coagulation factor C homolog) null allele exhibit vestibular dysfunction, hearing loss at the highest frequencies by 21 months. This mutant mouse strain may be useful in studies of late onset hearing loss.

Donating Investigator

Cynthia Morton, Brigham & Women's Hosp. , Harvard Med

Genetic overview

Genetic Background	Generation

Coch^tm1.1Stw

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Coch	cochlin

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Research Applications

Sensorineural Research
Neurobiology Research

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Details

Detailed Description

Homozygotes: Mice that are homozygous for the targeted mutation are viable, fertile and normal in size. Mice exhibit vestibular dysfunction by 13 and 21 months of age as determined by elevated measurements of the vestibular evoked potential (VsEP). Auditory brainstem response (ABR) testing at 21 months of age indicates hearing loss at the highest frequencies as determined by elevated or absent ABR thresholds. Histopathology at 21 months of age reveals no hair cell loss or obvious change in morphology. This mutant mouse strain may be useful in studies of late onset hearing loss.

Heterozygote:
Heterozygous mice do not have hearing loss, but exhibit the same vestibular malfunction at 21 months of age as the homozygous mice.

Development

A targeting vector was designed to insert a loxP site between exons 6 and 7 and an IRESlacZ cassette followed by a loxP-flanked PGKneo cassette into exon 12. The construct was electroporated into 129S1/Sv-Oca1⁺ Tyr⁺ Kitl⁺ -derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to a mixed C57BL/6 and CD1 background. Offspring were crossed a unknown background expressing Cre under the control of a beta actin promoter to remove exons 7 through 11 (containing two VWA domains) as well as the neo and lacZ cassettes and part of exon 12. Mice were subsequently crossed to CBA/CaJ for 12 generations. Upon arrival, mice were bred to CBA/CaJ for at least 1 generation to establish the colony.

Control Suggestions

000654 CBA/CaJ

Additional Information

Considerations for Choosing Controls

Selected References

Rodriguez CI; Cheng JG; Liu L; Stewart CL. 2004. Cochlin, a secreted von Willebrand factor type a domain-containing factor, is regulated by leukemia inhibitory factor in the uterus at the time of embryo implantation. Endocrinology 145(3):1410-8PubMed: 14657014 MGI: J:105566

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Genetics

Coch^tm1.1Stw

Allele Symbol: Coch^tm1.1Stw

Allele Name	targeted mutation 1.1, Colin L Stewart
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Coch^-
Gene Symbol and Name	Coch, cochlin
Gene Synonym(s)
Strain of Origin	129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Chromosome	12
Molecular Note	Exons 7-11 and part of exon 12, encoding the two vWA domains and remaining cochlin protein downstream of the LCCL domain, were removed via cre mediated recombination. Neither full length or truncated transcripts were detected in mutants.
Mutations Made By	Cynthia Morton, Brigham & Women's Hosp. , Harvard Med

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Sensorineural Research
- Hearing Defects
  - Age related hearing loss
Neurobiology Research
- Hearing Defects
  - Age related hearing loss

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Coch^tm1.1Stw/Coch^tm1.1Stw
involves: 129S1/Sv

normal phenotype

no abnormal phenotype detected
- Normal - at ~5 months, homozygotes do not display any apparent inner ear histopathology or any significant hearing loss relative to wild-type mice
- Normal - surprisingly, homozygotes are viable and overtly normal and females display no defects in implantation or reproduction relative to wild-type littermates

Genotype: Coch^tm1.1Stw/Coch^tm1.1Stw
involves: 129S1/Sv * C57BL/6 * CD-1

mammalian phenotype

hearing/vestibular/ear phenotype
- Normal - at P19, 3- and 5- months of age, homozygotes exhibit no significant differences in auditory brainstem responses to click and pure-tone stimuli (8, 16, 32 kHz) relative to wild-type mice

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

Genotype: Coch^tm1.1Stw/Coch^tm1.1Stw
CBACa.129S1-Coch

hearing/vestibular/ear phenotype

increased or absent threshold for auditory brainstem response
- increased threshold or absent at the highest frequency test (41.2 Hz) at 21 months of age

reduced linear vestibular evoked potential
- increase in VsEP thresholds at 13 and 21 months of age

mammalian phenotype

hearing/vestibular/ear phenotype
- Normal - despite hearing and vestibular deficits, no gross abnormalities are seen in the cochlear duct or its accessory structures

Genotype: Coch^tm1.1Stw/Coch⁺
CBACa.129S1-Coch

hearing/vestibular/ear phenotype

reduced linear vestibular evoked potential
- increase in VsEP thresholds at 21 months of age

mammalian phenotype

hearing/vestibular/ear phenotype
- Normal - unlike in homozygous mutant mice, no hearing deficit is detected at any age

References

Rodriguez CI; Cheng JG; Liu L; Stewart CL. 2004. Cochlin, a secreted von Willebrand factor type a domain-containing factor, is regulated by leukemia inhibitory factor in the uterus at the time of embryo implantation. Endocrinology 145(3):1410-8PubMed: 14657014 MGI: J:105566

Additional - Coch^tm1.1Stw related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Coch
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice are bred as homozygotes.
- Additional Breeding and Husbandry Support
Citation
When using the CBACa.129S1(Cg)-Coch^tm1.1Stw/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #34310 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

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

See MMRRC for Additional Conditions of Distribution

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:CBA/Ca.129S1(Cg)-Cochtm1.1Stw/Mmjax

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Cochtm1.1Stw

Allele Symbol: Cochtm1.1Stw

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Cochtm1.1Stw/Cochtm1.1Stwinvolves: 129S1/Sv

normal phenotype

Genotype: Cochtm1.1Stw/Cochtm1.1Stwinvolves: 129S1/Sv * C57BL/6 * CD-1

mammalian phenotype

Genotype: Cochtm1.1Stw/Cochtm1.1StwCBACa.129S1-Coch

hearing/vestibular/ear phenotype

mammalian phenotype

Genotype: Cochtm1.1Stw/Coch+CBACa.129S1-Coch

hearing/vestibular/ear phenotype

mammalian phenotype

References

Additional - Cochtm1.1Stw related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Also Known As:CBA/Ca.129S1(Cg)-Coch^tm1.1Stw/Mmjax

Coch^tm1.1Stw

Allele Symbol: Coch^tm1.1Stw

Genotype: Coch^tm1.1Stw/Coch^tm1.1Stw
involves: 129S1/Sv

Genotype: Coch^tm1.1Stw/Coch^tm1.1Stw
involves: 129S1/Sv * C57BL/6 * CD-1

Genotype: Coch^tm1.1Stw/Coch^tm1.1Stw
CBACa.129S1-Coch

Genotype: Coch^tm1.1Stw/Coch⁺
CBACa.129S1-Coch

Additional - Coch^tm1.1Stw related