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| These G117H BChE transgenic mice may be useful for biodefense and bioterrorism studies involving organophosphorus toxicants (such as the nerve agents sarin, soman, and VX, the antiglaucoma drug echothiophate, and the active metabolite of the insecticide parathion (paraoxon)) or as a model of the human Cynthiana variant of BChE (conferring succinylcholine resistance). | |||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Mutant Stock; Targeted Mutation; Transgenic; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote (Female x Male) Species laboratory mouse Donating Investigator Oksana Lockridge, Eppley Inst. (Univ of Nebraska Med Cntr) Description
Transgenic "G117H BChE" mice are viable and fertile. These mice express a mutant form of human butyrylcholinesterase (BCHE or BChE), harboring a single amino acid change at codon 117 (His for Gly), under the control of the ROSA26 promoter. This mutation has the unusual ability to hydrolyze organophosphorus toxicants (OP), as well as acetylcholine and is resistant to inhibition by OP. All tested tissues show G117H BChE enzymatic activity. In the founder mice and immediate offspring, plasma concentrations of the mutant protein are approximately 25% of endogenous wildtype mouse BChe. No reported abnormalities result from BChE overexpression in homozygous mutant mice. Transgenic mice injected with the OP echothiophate are protected from the severe toxicity and lethality observed in wildtype controls. This is the first transgenic mouse strain that expresses human BChE as well as the first mammal with hereditary OP resistance. These G117H BChE transgenic mice may be useful for biodefense and bioterrorism studies involving organophosphorus toxicants (such as the nerve agents sarin, soman, and VX, the antiglaucoma drug echothiophate, and the active metabolite of the insecticide parathion (paraoxon)) or as a model of the human Cynthiana variant of BChE (conferring succinylcholine resistance).The donating investigator has multiple strains available that may be useful for testing toxic compounds, including the AChE-deficient (Stock No. 005987), G117H BChE transgenic (Stock No. 007577), and BChE-deficient (see Stock No. 008077 and Stock No. 008087) mice.
Development
The transgene was designed with a G117H mutant human butyrylcholinesterase (BCHE, or BChE) cDNA sequence downstream of the Gt(ROSA)26Sor promoter. In detail, the human G117H BChE sequence (encoding the 28 amino acid signal peptide and 574 amino acid full-length protein) was modified with a single His for Gly amino acid mutation at codon 117 (G117H). To enhance the expression of the human G117H BChE, a chimeric intron (consisting of a human beta-globin gene and the branch point and 3' acceptor site from the intron of an immunoglobulin gene heavy chain variable region) was placed between the promoter and human G117H BChE sequence. A FLAG epitope tag (encoding amino acids DYKDDDDK) was placed at the carboxy-terminus of the human G117H BChE. The transgene also contained the human elongation factor 1-alpha poly(A) sequence at the 3' end. This transgene was microinjected into fertilized [C57BL/6 x (C57BL/6xSJL)F1] eggs. Founder mice (line M837T) were bred to B6SJL/F1Tac mice. Mutant mice were next bred together and/or to wildtype mice (either C57BL/6 or 129X1) for an unknown number of generations prior to arrival at The Jackson Laboratory.
Control Information
| Control | ||
|---|---|---|
| 100012 B6SJLF1/J | (approximate) | |
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Gt(ROSA)26Sor
View Strains carrying other alleles of Gt(ROSA)26Sor (47 strains)
Phenotype
Phenotype Information
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tg(Gt(ROSA)26Sor-BCHE*G117H)837Loc/Tg(Gt(ROSA)26Sor-BCHE*G117H)837Loc
involves: C57BL/6 * SJL
- homeostasis/metabolism phenotype
- abnormal enzyme/ coenzyme level (MGI Ref ID J:89332)
- F5 generation mice express human butyrylcholinesterase BCHE protein at 25% the level of the endogenous mouse protein
This mouse can be used to support research in many areas including:
Cancer Research
Toxicology
Metabolism Research
Neurobiology Research
Neuromuscular Defects
Neurotransmitter Receptor and Synaptic Vesicle Defects
Receptor Defects (cholinergic receptor)
Tremor Defects
Research Tools
Cancer Research
Metabolism Research
Neurobiology Research
Sensorineural Research
Toxicology Research (drug metabolism)
Toxicology Research (drug/compound testing)
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Tg(Gt(ROSA)26Sor-BCHE*G117H)837Loc | ||
|---|---|---|---|
| Allele Name | transene insertion 837, Oksana Lockridge | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | G117H BChE; M844T; | ||
| Strain of Origin | C57BL/6 x (C57BL/6 x SJL)F1 | ||
| Expressed Gene | BCHE, butyrylcholinesterase, human | ||
| Promoter | Gt(ROSA)26Sor, gene trap ROSA 26, Philippe Soriano, mouse, laboratory | ||
| Molecular Note | The human G117H BChE sequence (encoding the 28 amino acid signal peptide and 574 amino acid full-length protein) was modified with a single His for Gly amino acid mutation at codon 117 (G117H). To enhance expression, a chimeric intron (consisting of a human beta-globin gene and the branch and 3' acceptor site from the intron of an immunoglobulin gene heavy chain variable region) was placed between the promoter and human G117H BChE sequence. A FLAG epitope tag (encoding amino acids DYKDDDDK) was placed atthe carboxy-terminus of the human G117H BChE. The transgene also contained the human elongation factor 1-alpha poly(A) sequence at the 3' end. This transgene was microinjected into fertilized [C57BL/6 x (C57BL/6xSJL)F1] eggs. Founder mice (line M837T) were bred to B6SJL/F1Tac mice. All tested tissues express G117H BChE enzyme activity. In addition, 2 other stable lines M844T and M853T were generated, with detailed analysis of M844T described. [MGI Ref ID J:89332] | ||
| Gene Symbol and Name | Tg(Gt(ROSA)26Sor-BCHE*G117H)837Loc, transene insertion 837, Oksana Lockridge | ||
| Chromosome | UN | ||
| Gene Common Name(s) | G117H BChE; M844T; | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(Gt(ROSA)26Sor-BCHE*G117H)837Loc, QPCR, vers. 2
Tg(Gt(ROSA)26Sor-BCHE*G117H)837Loc, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Wang Y; Boeck AT; Duysen EG; Van Keuren M; Saunders TL; Lockridge O. 2004. Resistance to organophosphorus agent toxicity in transgenic mice expressing the G117H mutant of human butyrylcholinesterase. Toxicol Appl Pharmacol 196(3):356-66. [PubMed: 15094306] [MGI Ref ID J:89332]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX12
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, homozygous mice may be bred. Mating System Homozygote x Homozygote (Female x Male) Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $203.80 Female or Male Homozygous for Tg(Gt(ROSA)26Sor-BCHE*G117H)837Loc *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $407.60 Homozygous for Tg(Gt(ROSA)26Sor-BCHE*G117H)837Loc x Homozygous for Tg(Gt(ROSA)26Sor-BCHE*G117H)837Loc
Additional Supply Details
| Supply Notes |
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| Pricing for International shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $265.00 Female or Male Homozygous for Tg(Gt(ROSA)26Sor-BCHE*G117H)837Loc *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $529.90 Homozygous for Tg(Gt(ROSA)26Sor-BCHE*G117H)837Loc x Homozygous for Tg(Gt(ROSA)26Sor-BCHE*G117H)837Loc
Additional Supply Details
| Supply Notes |
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Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| 100012 B6SJLF1/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. | ||
General Terms and Conditions
See Terms of Use
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.Ordering and Purchasing Information
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