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B6.Cg-RhoTvrm4/Pjn
Stock No: 029087 | Tvrm4
  • Chemically Induced Mutation
  • Congenic
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  • Details
    • Detailed Description
    • Development
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    • Selected References
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  • Disease/Phenotype
    • Disease Terms
    • Research Areas By Phenotype
    • Mammalian Phenotype Terms by Genotype
    • References
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Overview

Also Known As:Tvrm4

This point substitution of asparagine in place of a conserved isoleucine in the last of seven transmembrane domains of rhodopsin makes heterozygotes highly sensitive to light-induced photoreceptor degeneration, although there is no loss of photoreceptor cell bodies at 1 year of age when maintained in standard housing conditions without bright light exposure. This provides a slightly less severe model of Retinitis Pigmentosa 4 than the RhoTvrm1 allele.

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Genetic overview

Genetic Background Generation
000664 C57BL/6J

RhoTvrm4

Allele Type Gene Symbol Gene Name
Chemically induced (ENU) (Not Specified) Rho rhodopsin
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Research Applications

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Base Price

Starting at:

$249.86 Domestic price for female
320.17 Domestic price for breeder pair
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Details

Detailed Description

RhoTvrm4 heterozygotes are highly sensitive to light-induced photoreceptor degeneration, but when maintained in standard conditions with ambient light no loss of photoreceptor cell bodies was detected at 1 year of age and immunohistochemistry showed proper localization of rhodopsin to the outer segments. At 4 months of age the outer segment lengths are normal but at 1 year they are slightly shorter. Assessment by dark-adapted ERG found no reduction in the amplitude of alpha or beta waves in heterozygotes at 4 months or 1 year of age. Light-adapted ERGs also found no statistically significant abnormalities in beta wave amplitude. However, within one hour after a five-minute exposure to 12,000 lux of bright light the photoreceptor outer segment appears disorganized, there are areas either devoid of outer segments or having aggregates, and the apical processes of retinal pigment epithelium appear to extend further along the outer segments than normal. After 24 hours of exposure the inner and outer segments of the retina are disorganized, the border between them indiscernible, and apoptotic photoreceptor cells can be identified by TUNEL staining. One week after exposure photoreceptor degeneration has progressed extensively so that only 2 or fewer layers of photoreceptor nuclei remain. A two-minute exposure to 12,000 lux was found to be adequate to induce photoreceptor degeneration in two of three heterozygotes. Phototransduction deactivation is similar to that of wild-type controls in a two-flash ERG protocol, but heterozygotes have deficits in recovery of the a-wave from bleaching light.

Development

The RhoTvrm4 mutation was induced by ethylnitrosourea in an ES cell derived from (129S4/SvJae x C57BL/6J)F1and backcrossed onto the C57BL/6J background by repeated cycles of backcrossing.

Control Suggestions

  • Wild-type from the colony

Approximate Controls

  • 000664 C57BL/6J

Additional Information

  • Considerations for Choosing Controls

Selected References

  • Budzynski E; Gross AK; McAlear SD; Peachey NS; Shukla M; He F; Edwards M; Won J; Hicks WL; Wensel TG; Naggert JK; Nishina PM. 2010. Mutations of the opsin gene (Y102H and I307N) lead to light-induced degeneration of photoreceptors and constitutive activation of phototransduction in mice. J Biol Chem 285(19):14521-33PubMed: 20207741MGI: J:159523
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Genetics

RhoTvrm4

Allele Symbol: RhoTvrm4

Allele Name translational research vision model 4
Allele Type Chemically induced (ENU) (Not Specified)
Allele Synonym(s) I307N Rho
Gene Symbol and Name Rho, rhodopsin
Gene Synonym(s)
Strain of Origin (129S4/SvJae x C57BL/6J)F1
Chromosome 6
Molecular Note A missense mutation changes amino acid 307, isoleucine (ATC), to asparagine (AAC). Ile-307 is located in the 7th transmembrane region of RHO and is conserved across species, including human, primate, cat, dog, and rat.

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).

  • retinitis pigmentosa 4

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: RhoTvrm4/Rho+
B6.Cg-Rho/Pjn

cellular phenotype

  • increased retinal apoptosis
    • TUNEL+ photoreceptors
    • (MGI Ref ID J:159523)

pigmentation phenotype

  • abnormal retinal pigment epithelium morphology
    • after exposure to 12,000 lux of bright light, apical processes of retinal pigment epithelium that normally ensheath the outer segments appear to extend further along the outer segments than in wild-type
    • (MGI Ref ID J:159523)

vision/eye phenotype

  • abnormal photoreceptor outer segment morphology
    • 1 h after exposure to 12,000 lux of bright light, appear disorganized and some areas are devoid of outer segments, whereas others appear to contain outer segment aggregates
    • (MGI Ref ID J:159523)
    • slightly shorter at 1 year of age
    • (MGI Ref ID J:159523)
  • disorganized photoreceptor inner segment
    • the border between the outer and inner segments of the retina, and both compartments are highly disorganized 24 h after exposure to 12,000 lux of bright light
    • (MGI Ref ID J:159523)
  • disorganized retinal outer nuclear layer
    • 24 h after exposure to 12,000 lux of bright light the outer nuclear layer appears disorganized, although cell loss is not apparent
    • (MGI Ref ID J:159523)
  • retinal outer nuclear layer degeneration
    • two or fewer layers of photoreceptor nuclei remaining at 1 week following light exposure
    • (MGI Ref ID J:159523)
  • disorganized photoreceptor outer segment
    • the border between the outer and inner segments of the retina, and both compartments are highly disorganized 24 h after exposure to 12,000 lux of bright light
    • (MGI Ref ID J:159523)
  • retinal photoreceptor degeneration
    • bright light-induced degeneration of photoreceptors
    • (MGI Ref ID J:159523)
    • Normal - however, under standard housing conditions no degeneration is detected
    • (MGI Ref ID J:159523)
    • exposure to 12,000 lux for 2 or more minutes induces photoreceptor degeneration
    • (MGI Ref ID J:159523)
  • photosensitivity
    • exposure to 12,000 lux for 2 or more minutes induces photoreceptor degeneration
    • (MGI Ref ID J:159523)
    • exposure to 12,000 lux of light for 5 min leads to visible bleaching of the entire retina for 1 h following exposure, in contrast wild-type retinas are unaffected
    • (MGI Ref ID J:159523)
  • abnormal retinal pigment epithelium morphology
    • after exposure to 12,000 lux of bright light, apical processes of retinal pigment epithelium that normally ensheath the outer segments appear to extend further along the outer segments than in wild-type
    • (MGI Ref ID J:159523)
  • delayed dark adaptation
    • mice recover with a time constant of 9.5 min and reach an asymptote that is only 60% of the dark adapted value
    • (MGI Ref ID J:159523)
  • increased retinal apoptosis
    • TUNEL+ photoreceptors
    • (MGI Ref ID J:159523)

homeostasis/metabolism phenotype

  • photosensitivity
    • exposure to 12,000 lux of light for 5 min leads to visible bleaching of the entire retina for 1 h following exposure, in contrast wild-type retinas are unaffected
    • (MGI Ref ID J:159523)
    • exposure to 12,000 lux for 2 or more minutes induces photoreceptor degeneration
    • (MGI Ref ID J:159523)
  • abnormal retinol level
    • Normal - however, no difference is detected at 1 h after light exposure
    • (MGI Ref ID J:159523)
    • extracts of whole eyes collected immediately after exposure to 12,000 lux for 5 mins contain significantly lower levels of all trans-retinol than in wild-type
    • (MGI Ref ID J:159523)

nervous system phenotype

  • abnormal photoreceptor outer segment morphology
    • 1 h after exposure to 12,000 lux of bright light, appear disorganized and some areas are devoid of outer segments, whereas others appear to contain outer segment aggregates
    • (MGI Ref ID J:159523)
    • slightly shorter at 1 year of age
    • (MGI Ref ID J:159523)
  • disorganized photoreceptor inner segment
    • the border between the outer and inner segments of the retina, and both compartments are highly disorganized 24 h after exposure to 12,000 lux of bright light
    • (MGI Ref ID J:159523)
  • disorganized photoreceptor outer segment
    • the border between the outer and inner segments of the retina, and both compartments are highly disorganized 24 h after exposure to 12,000 lux of bright light
    • (MGI Ref ID J:159523)
  • retinal photoreceptor degeneration
    • Normal - however, under standard housing conditions no degeneration is detected
    • (MGI Ref ID J:159523)
    • bright light-induced degeneration of photoreceptors
    • (MGI Ref ID J:159523)
    • exposure to 12,000 lux for 2 or more minutes induces photoreceptor degeneration
    • (MGI Ref ID J:159523)

References

  • Budzynski E; Gross AK; McAlear SD; Peachey NS; Shukla M; He F; Edwards M; Won J; Hicks WL; Wensel TG; Naggert JK; Nishina PM. 2010. Mutations of the opsin gene (Y102H and I307N) lead to light-induced degeneration of photoreceptors and constitutive activation of phototransduction in mice. J Biol Chem 285(19):14521-33PubMed: 20207741MGI: J:159523

Additional - RhoTvrm4 related

Technical Support

CONTACT TECHNICAL SUPPORT
  • Genotyping Protocols

    • Sanger sequencing:Rho
    • Genotyping resources and troubleshooting
  • Mating System

    • Heterozygote x +/+ sibling
    • +/+ sibling x Heterozygote
  • Citation

    When using the Tvrm4 mouse strain in a publication, please cite the originating article(s) and include JAX stock #029087 in your Materials and Methods section.

Pricing & Availability

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Live Mouse

Age Genotype Price
weeks

Breeder Pair

Sex Genotype Price
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Male

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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.

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