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| These SAC-GFP transgenic mice may be useful as a cancer-resistant model; evading oncogene-mediated tumorigenesis by expressing an archetypical anticancer therapeutic agent (SAC) that is well tolerated in vivo, does not compromise the normal tissue function or life span of the host, and is potent enough at physiologically innocuous levels to concomitantly suppress the NF-kappaB pro-cell survival pathway and induce tumor suppression via apoptosis. | |||||||||
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Description
Strain Information
Former Names B6;C3-Tg(ACTB-SAC/EGFP)35Rang/J (Changed: 08-MAY-08 ) B6;C3-Tg(ACTB-Pawr/EGFP)35Rang/J (Changed: 29-FEB-08 ) Type Mutant Stock; Transgenic; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Donating Investigator Vivek Rangnekar, University of Kentucky Description
Hemizygous SAC transgenic mice have normal fertility, viability, and aging. Widespread expression of the transgene is observed in all tested tissues (with some differential tissue-specific regulation of transgene expression or protein stability reported). The SAC-GFP fusion protein is composed of the cancer-specific proapoptotic effector domain (or SAC domain) of the Par-4 gene fused to an enhanced green fluorescent protein (EGFP). As a result, SAC-GFP transgenic mice have increased resistance to spontaneous liver/spleen and TRAMP-induced prostate tumor development. The protective nature of the transgene appears to be linked to inhibition of NF-kappaB activity and induction of apoptosis. Cells derived from SAC transgenic mice grow normally in short-term culture and presence of the SAC transgene prevents oncogene-mediated cellular transformation. The donating investigator reports that EGFP expression is appropriate for immunoblots, but not sufficient enough for fluorescence of flow cytometry applications. These SAC-GFP transgenic mice may be useful as a cancer-resistant model; evading oncogene-mediated tumorigenesis by expressing an archetypical anticancer therapeutic agent (SAC) that is well tolerated in vivo, does not compromise the normal tissue function or life span of the host, and is potent enough at physiologically innocuous levels to concomitantly suppress the NF-kappaB pro-cell survival pathway and induce tumor suppression via apoptosis.Development
The pCA/SAC-GFP transgene was designed with a chicken beta-actin promoter (and cytomegalovirus (CMV) enhancer) upstream of a fusion gene containing a Par-4 SAC domain (Pawr gene, amino acids 137-195) cDNA fused to an enhanced green fluorescent protein (EGFP), all followed by a polyA sequence. This transgene was microinjected into pronuclei of fertilized B6C3F1 oocytes, and the resulting transgenic offspring were bred to B6C3F1 mice. Founder line 35 mice (SAC/35; found to have 6-8 copies of the transgene) were bred with B6C3F1 mice. These SAC/35 mice were maintained on a mixed B6C3 genetic background by sibling intercross for many generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred with B6C3F1 (Stock No. 100010) to establish the colony.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 100010 B6C3F1/J | (approximate) | |
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of ACTB
View Strains carrying other alleles of ACTB (34 strains)
Additional Web Information
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
assigned by genotype
Tg(CAG-SAC/EGFP)35Rang/0
involves: C3H * C57BL/6
- life span-post-weaning/aging
- *normal* life span-post-weaning/aging (MGI Ref ID J:125633)
- mice display normal lifespan compared to wild-type mice
- tumorigenesis
- increased resistance to tumor development (MGI Ref ID J:125633)
- transgenic mice do not develop spontaneous liver tumors or splenic lymphomas in contrast to wild-type controls
- no mice develop prostatic neoplasms
- increased resistance to liver neoplasm (MGI Ref ID J:125633)
- mice do not develop spontaneous hepatocarcinomas or lymphomas in contrast to control wild-type B6C3 hybrid mice and mice expressing only a GFP transgene which develop such liver tumors by ~18 months of age
- increased resistance to lymphoma (MGI Ref ID J:125633)
- transgenic mice do not develop spontaneous splenic lymphomas, in contrast to wild-type controls
- liver/biliary system phenotype
- *normal* liver/biliary system phenotype (MGI Ref ID J:125633)
- liver architecture is normal in mice resistant to tumor development
- hematopoietic system phenotype
- *normal* hematopoietic system phenotype (MGI Ref ID J:125633)
- spleen morphology and architecture is normal in mice
- reproductive system phenotype
- *normal* reproductive system phenotype (MGI Ref ID J:125633)
- transgenic mice have normal-sized litters and both sexes display normal level of fertility
- endocrine/exocrine gland phenotype
- *normal* endocrine/exocrine gland phenotype (MGI Ref ID J:125633)
- prostate glands are normal
This mouse can be used to support research in many areas including:
GFP relatedApoptosis Research
Endogenous Regulators
Cancer Research
Genes Regulating Growth and Proliferation
Growth Factors/Receptors/Cytokines
Tumor Resistance
Tumor Suppressor Genes
Cell Biology Research
Genes Regulating Growth and Proliferation
Signal Transduction
Transcriptional Regulation
Research Tools
Apoptosis Research
Cancer Research (anti-tumor activity)
Cell Biology Research
Fluorescent Proteins
Research Tools
Fluorescent Proteins
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(CAG-SAC/EGFP)35Rang | ||
|---|---|---|---|
| Allele Name | transgene insertion 35, Vivek Rangnekar | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | SAC-GFP line 35; SAC/35; Tg(ACTB-SAC/EGFP)35Rang; | ||
| Mutation Made By | Vivek Rangnekar, University of Kentucky | ||
| Strain of Origin | (C57BL/6 x C3H)F1 | ||
| Expressed Gene | Pawr, PRKC, apoptosis, WT1, regulator, mouse, laboratory | ||
| Expressed Gene | GFP, Green Fluorescent Protein, jellyfish | ||
| Green Fluorescent Protein (GFP), derived from the jellyfish Aequorea victoria, is a versatile reporter molecule which has found use in many biological applications. In some constructs the original molecule has been modified in order to enhance its fluorescence intensity (EGFP, enhanced GFP). When utilized in a transgenic construct, tissue expressing sufficient amounts of GFP will fluoresce when exposed to a 488 nm light source. | |||
| Promoter | ACTB, actin, beta, chicken | ||
| Molecular Note | The pCA/SAC-GFP transgene was designed with a chicken beta-actin promoter (and cytomegalovirus (CMV) enhancer) upstream of a fusion gene containing a Par-4 SAC domain (Pawr gene, amino acids 137-195) cDNA fused to an enhanced green fluorescent protein (EGFP), all followed by a polyA sequence. The resulting transgenic offspring were bred to (C57BL/6 x C3H)F1 mice. Founder line 35 mice (SAC/35; found to have 6-8 copies of the transgene). Widespread expression of the transgene is observed in all tested tissues (with some differential tissue-specific regulation of transgene expression or protein stability reported). EGFP expression level is appropriate for immunoblots, but not sufficient enough for fluorescence of flow cytometry applications. [MGI Ref ID J:125633] | ||
Genotyping
Genotyping Information
This strain will not have a genotyping protocol or one is not currently available.
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Zhao Y; Burikhanov R; Qiu S; Lele SM; Jennings CD; Bondada S; Spear B; Rangnekar VM. 2007. Cancer resistance in transgenic mice expressing the SAC module of Par-4. Cancer Res 67(19):9276-85. [PubMed: 17909035] [MGI Ref ID J:125633]
Health & husbandry
Health & Colony Maintenance Information
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, hemizygotes may be bred to wildtype siblings or to B6C3F1/J (Stock No. 100010) inbred mice.
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
This strain is currently Under Development for Distribution Colony.
To register your interest in this strain go to the Strain Interest Form.
Estimated Available for Sale Date:
Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.
View All Strains Under Development and On Hold
Supply Details
| Standard Supply | Under Development for Distribution Colony |
|---|---|
| Supply Notes |
|
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 100010 B6C3F1/J | (approximate) | |
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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