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.
Vsevolod V. Gurevich, Vanderbilt University
Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Sag | S-antigen, retina and pineal gland (arrestin) |
Allele Type |
---|
Transgenic (Inserted expressed sequence) |
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.
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-Sagtm1Jnc 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.
Expressed Gene | Sag, S-antigen, retina and pineal gland (arrestin), mouse, laboratory |
---|---|
Site of Expression |
Allele Name | targeted mutation 1, Jeannie Chen |
---|---|
Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | arr1-; Arrb1tm1Jnc; 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 |
Allele Name | transgene insertion 50, Vsevolod Gurevich |
---|---|
Allele Type | Transgenic (Inserted expressed sequence) |
Allele Synonym(s) | 3A-50; Tg(Rho-Sag*)1Seva; Tg(Sag*3A50)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. |
While maintaining a live colony, these mice are bred as homozygous for the targeted mutation and hemizygous for the transgene.
When using the B6.129S-Sagtm1Jnc 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.
Facility Barrier Level Descriptions
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.
What information were you hoping to find through your search?
How easy was it to find what you were looking for?
We may wish to follow up with you. Enter your email if you are happy for us to connect and reachout to you with more questions.
Please Enter a Valid Email Address
Thank you for sharing your feedback! We are working on improving the JAX Mice search. Come back soon for exciting changes.