Overview

Sag -/- (retinal S-antigen) mice develop disorganized photoreceptors and retinal degeneration when raised in cyclic light, when combined with the high-expressing (3A-50) mutant arrestin (Sag) transgenics, the transgene rescues a portion of the KO phenotype preventing photoreceptor loss, but does not return outer segment length completely to wild-type levels. This mutant mouse strain may be useful in studies of retinal degeneration, light-dark adaptation and G protein-coupled receptor signaling.

Donating Investigator

Vsevolod V. Gurevich, Vanderbilt University

Genetic overview

Genetic Background	Generation

Sag^tm1Jnc

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Sag	S-antigen, retina and pineal gland (arrestin)

Tg(Rho-Sag*)50Seva

Allele Type
Transgenic (Inserted expressed sequence)

View Genetics

Research Applications

Sensorineural Research

View All Research Applications

Details

Detailed Description

Retinal S-antigen (Sag or arrestin) has a high affinity for phosphorylated rhodopsin, but a low affinity for unphosphorylated rhodopsin. Arrestin binds to phosphorylated rhodopsin and blocks interaction with the G protein transducin, halting the phototransduction cascade.Mice that are homozygous for the targeted mutation develop disorganized photoreceptors and retinal degeneration when raised in cyclic light. Retinal degeneration is characterized by a progressive decrease in photoreceptor outer segment (OS) length and by progressive thinness of the outer nuclear layer (ONL). The 3A-50 transgene is altered to bind unphosphorylated rhodopsin and expresses mutant arrestin at 50% of wild type. When Sag -/- mice are combined with the low-expressing (3A-50) mutant arrestin (Sag) transgenics, the transgene rescues a portion of the KO phenotype preventing photoreceptor loss, but does not return OS length completely to wild-type levels.

This mutant mouse strain may be useful in studies of retinal degeneration, light-dark adaptation and G protein-coupled receptor signaling.

Development

The transgenic construct contains three amino acid substitutions - Leu374Ala, Val375Ala, and Phe376Ala - introduced into the mouse retinal S-antigen (arrestin) coding sequence under the direction of the opsin promoter. The amino acid substitutions replace the three bulky hydrophobic residues that anchor the C tail to the body of the molecule with alanines. The transgene was microinjected into fertilized C57BL/6 oocytes and founder mice were crossed to C57BL/6 mice for an unknown number of generations. Founder line 50 expresses arrestin at 50% of wild type. Mice were crossed to B6.129S-Sag^tm1Jnc mice to generate mice that are heterozygous for the targeted mutation and hemizygous for the transgene. The colony was maintained as a backcross to C57BL/6. Upon arrival, mice were bred to C57BL/6J mice to establish the colony.

Expression Data

Expressed Gene	Sag, S-antigen, retina and pineal gland (arrestin), mouse, laboratory
Site of Expression

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Nair KS; Hanson SM; Mendez A; Gurevich EV; Kennedy MJ; Shestopalov VI; Vishnivetskiy SA; Chen J; Hurley JB; Gurevich VV; Slepak VZ. 2005. Light-dependent redistribution of arrestin in vertebrate rods is an energy-independent process governed by protein-protein interactions. Neuron 46(4):555-67PubMed: 15944125 MGI: J:99855
Song X; Vishnivetskiy SA; Gross OP; Emelianoff K; Mendez A; Chen J; Gurevich EV; Burns ME; Gurevich VV. 2009. Enhanced arrestin facilitates recovery and protects rods lacking rhodopsin phosphorylation. Curr Biol 19(8):700-5PubMed: 19361994 MGI: J:148930

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Genetics

Sag^tm1Jnc

Allele Symbol: Sag^tm1Jnc

Allele Name	targeted mutation 1, Jeannie Chen
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	arr1-; Arrb1^tm1Jnc; arrestin^-
Gene Symbol and Name	Sag, S-antigen, retina and pineal gland (arrestin)
Gene Synonym(s)
Strain of Origin	129S/SvEv
Chromosome	1
Molecular Note	Part of the 5' promoter and exons 1 and 2 were replaced with a neomycin resistance cassette via homologous recombination. Gene expression was undetectable in rod cells of homozygous mutant animals as shown by Western blot analysis.
Mutations Made By	Jeannie Chen, University of Southern California

Tg(Rho-Sag*)50Seva

Allele Symbol: Tg(Rho-Sag*)50Seva

Allele Name	transgene insertion 50, Vsevolod Gurevich
Allele Type	Transgenic (Inserted expressed sequence)
Allele Synonym(s)	3A-50; Tg(Rho-Sag)1Seva; Tg(Sag3A50)1Seva
Gene Symbol and Name	Tg(Rho-Sag*)50Seva, transgene insertion 50, Vsevolod Gurevich
Gene Synonym(s)
Promoter	Rho, rhodopsin, mouse, laboratory
Expressed Gene	Sag, S-antigen, retina and pineal gland (arrestin), mouse, laboratory
Strain of Origin	C57BL/6
Chromosome	UN
Molecular Note	The transgenic construct contains three amino acid substitutions (Leu374Ala, Val375Ala, and Phe376Ala) introduced into the mouse retinal S-antigen (arrestin; (GenBank M24086)) coding sequence under the direction of the mouse rod opsin promoter. Line 1 and 2 with moderate and high expression were generated from founders 3A50 and 3A240, respectively.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Sensorineural Research
- Retinal Degeneration

Mammalian Phenotype Terms by Genotype

References

Nair KS; Hanson SM; Mendez A; Gurevich EV; Kennedy MJ; Shestopalov VI; Vishnivetskiy SA; Chen J; Hurley JB; Gurevich VV; Slepak VZ. 2005. Light-dependent redistribution of arrestin in vertebrate rods is an energy-independent process governed by protein-protein interactions. Neuron 46(4):555-67PubMed: 15944125 MGI: J:99855
Song X; Vishnivetskiy SA; Gross OP; Emelianoff K; Mendez A; Chen J; Gurevich EV; Burns ME; Gurevich VV. 2009. Enhanced arrestin facilitates recovery and protects rods lacking rhodopsin phosphorylation. Curr Biol 19(8):700-5PubMed: 19361994 MGI: J:148930

Additional - Sag^tm1Jnc related

Additional - Tg(Rho-Sag*)50Seva related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Sanger sequencing:** Sag*L374A,V375A,F376A
- Separated PCR:Tg(Rho-Sag*)240Seva-alternate1
- Separated PCR:Sag
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice are bred as homozygous for the targeted mutation and hemizygous for the transgene.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129S-Sag^tm1Jnc Tg(Rho-Sag*)50Seva/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #36458 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

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Sagtm1Jnc

Allele Symbol: Sagtm1Jnc

Tg(Rho-Sag*)50Seva

Allele Symbol: Tg(Rho-Sag*)50Seva

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

References

Additional - Sagtm1Jnc related

Additional - Tg(Rho-Sag*)50Seva 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

Sag^tm1Jnc

Allele Symbol: Sag^tm1Jnc

Additional - Sag^tm1Jnc related