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| These Gαq-40 mice are hemizygous for the Gnaq allele with overexpression of Gαq in the heart. These mice may be useful for studying the biochemical and physiologic phenotype resembling both the compensated and decompensated phases of human cardiac hypertrophy. | |||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
Strain Information
Type Coisogenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Noncarrier x Hemizygote (Female x Male) 27-JUL-10 Species laboratory mouse Generation F?+F3 (12-JUL-11)
Generation DefinitionsDonating Investigator Gerald Dorn, Washington University School of Medicine Description
Mice hemizygous for the Myh6-Gnaq allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. The donating investigator states that hemizygous females develop peripartum cardiomyopathy. Expression of Gαq is regulated by an α-myosin heavy chain (Myh6) promoter, which leads to overexpression of Gαq in the heart. This overexpression results in cardiac hypertrophy, defined as a conserved program of fetal gene expression, increased heart weight, and increased cardiomyocyte size, which severely compromises systolic cardiac function, and results in overt cardiac failure. Upon experimental pressure overloading, the mice progress rapidly to heart failure. These mice may be useful for studying the biochemical and physiologic phenotype resembling both the compensated and decompensated phases of human cardiac hypertrophy.Development
A transgenic vector was generated including the entire coding region of the GTP-binding proteins class Gq protein subunit Gaq (Gnaq) gene under control of an α-myosin heavy chain (Myh6) promoter, followed by a simian virus 40 intron and a polyadenylation signal (polyA). The construct was microinjected into FVB/N fertilized oocytes, and founder mice were bred to FVB/N. Mice from founder line 40 (Gαq-40) were identified to establish a hemizygous colony. Upon arrival at The Jackson Laboratory, transgenic mice were bred to FVB/NJ inbred mice (Stock No. 001800) for at least one generation to establish the colony.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Myh6
View Strains carrying other alleles of Myh6 (38 strains)
Phenotype
Phenotype Information
assigned by genotype
Tg(Myh6-Gnaq)40Gwd/0
involves: FVB/N
- mortality/aging
- premature death
- most die by 5 weeks of age (MGI Ref ID J:41949)
This mouse can be used to support research in many areas including:
Cardiovascular Research
Heart Abnormalities
cardiomyopathy
Developmental Biology Research
Internal/Organ Defects
heart
Internal/Organ Research
Heart Abnormalities
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Tg(Myh6-Gnaq)40Gwd | ||
|---|---|---|---|
| Allele Name | transgene insertion 40, Gerald W Dorn II | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | Galphaq-40; Tg(Myh6-Gnaq)2Gwd; Tg(Myhca-Gnaq)2Gwd; | ||
| Mutation Made By | Gerald Dorn, Washington University School of Medicine | ||
| Strain of Origin | FVB/N | ||
| Expressed Gene | Gnaq, guanine nucleotide binding protein, alpha q polypeptide, mouse, laboratory | ||
| Promoter | Myh6, myosin, heavy polypeptide 6, cardiac muscle, alpha, murine, murine | ||
| Molecular Note | A 1.46 kb mouse Gnaq cDNA sequence under regulatory control of a full length mouse Myhca promoter was used for the transgene. The mouse Myhca promoter was used to drive transgene expression in the heart. Transgenic line designated Galphaq-40 carries 40 copies of the transgene. [MGI Ref ID J:41949] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(Myh6-Gnaq)MCA,Separated MCA
Tg(Myh6-Gnaq)MCA, Melt Curve Analysis
Tg(Myh6-Gnaq), Separated PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
D'Angelo DD; Sakata Y; Lorenz JN; Boivin GP; Walsh RA; Liggett SB ; Dorn GW 2nd. 1997. Transgenic Galphaq overexpression induces cardiac contractile failure in mice. Proc Natl Acad Sci U S A 94(15):8121-6. [PubMed: 9223325] [MGI Ref ID J:41949]
Additional References
Tg(Myh6-Gnaq)40Gwd relatedBiolo A; Greferath R; Siwik DA; Qin F; Valsky E; Fylaktakidou KC; Pothukanuri S; Duarte CD; Schwarz RP; Lehn JM; Nicolau C; Colucci WS. 2009. Enhanced exercise capacity in mice with severe heart failure treated with an allosteric effector of hemoglobin, myo-inositol trispyrophosphate. Proc Natl Acad Sci U S A 106(6):1926-9. [PubMed: 19204295] [MGI Ref ID J:144938]
Dorn GW 2nd; Tepe NM; Lorenz JN; Koch WJ; Liggett SB. 1999. Low- and high-level transgenic expression of beta2-adrenergic receptors differentially affect cardiac hypertrophy and function in Galphaq- overexpressing mice. Proc Natl Acad Sci U S A 96(11):6400-5. [PubMed: 10339599] [MGI Ref ID J:55199]
Lancel S; Qin F; Lennon SL; Zhang J; Tong X; Mazzini MJ; Kang YJ; Siwik DA; Cohen RA; Colucci WS. 2010. Oxidative posttranslational modifications mediate decreased SERCA activity and myocyte dysfunction in Galphaq-overexpressing mice. Circ Res 107(2):228-32. [PubMed: 20508180] [MGI Ref ID J:175046]
Rogers JH; Tsirka A; Kovacs A; Blumer KJ; Dorn GW 2nd; Muslin AJ. 2001. RGS4 reduces contractile dysfunction and hypertrophic gene induction in Galpha q overexpressing mice. J Mol Cell Cardiol 33(2):209-18. [PubMed: 11162127] [MGI Ref ID J:127759]
Roth DM; Bayat H; Drumm JD; Gao MH; Swaney JS; Ander A; Hammond HK. 2002. Adenylyl cyclase increases survival in cardiomyopathy. Circulation 105(16):1989-94. [PubMed: 11997288] [MGI Ref ID J:133188]
Roth DM; Gao MH; Lai NC; Drumm J; Dalton N; Zhou JY; Zhu J; Entrikin D; Hammond HK. 1999. Cardiac-directed adenylyl cyclase expression improves heart function in murine cardiomyopathy. Circulation 99(24):3099-102. [PubMed: 10377071] [MGI Ref ID J:133194]
Satoh M; Matter CM; Ogita H; Takeshita K; Wang CY; Dorn GW 2nd; Liao JK. 2007. Inhibition of apoptosis-regulated signaling kinase-1 and prevention of congestive heart failure by estrogen. Circulation 115(25):3197-204. [PubMed: 17562954] [MGI Ref ID J:137560]
Song Q; Schmidt AG; Hahn HS; Carr AN; Frank B; Pater L; Gerst M; Young K; Hoit BD; McConnell BK; Haghighi K; Seidman CE; Seidman JG; Dorn GW 2nd; Kranias EG. 2003. Rescue of cardiomyocyte dysfunction by phospholamban ablation does not prevent ventricular failure in genetic hypertrophy. J Clin Invest 111(6):859-67. [PubMed: 12639992] [MGI Ref ID J:82521]
Takimoto E; Koitabashi N; Hsu S; Ketner EA; Zhang M; Nagayama T; Bedja D; Gabrielson KL; Blanton R; Siderovski DP; Mendelsohn ME; Kass DA. 2009. Regulator of G protein signaling 2 mediates cardiac compensation to pressure overload and antihypertrophic effects of PDE5 inhibition in mice. J Clin Invest 119(2):408-20. [PubMed: 19127022] [MGI Ref ID J:146192]
Tepe NM; Liggett SB. 1999. Transgenic replacement of type V adenylyl cyclase identifies a critical mechanism of beta-adrenergic receptor dysfunction in the G alpha q overexpressing mouse. FEBS Lett 458(2):236-40. [PubMed: 10481072] [MGI Ref ID J:57726]
Timofeyev V; He Y; Tuteja D; Zhang Q; Roth DM; Hammond HK; Chiamvimonvat N. 2006. Cardiac-directed expression of adenylyl cyclase reverses electrical remodeling in cardiomyopathy. J Mol Cell Cardiol 41(1):170-81. [PubMed: 16750219] [MGI Ref ID J:110971]
Timofeyev V; Porter CA; Tuteja D; Qiu H; Li N; Tang T; Singapuri A; Han PL; Lopez JE; Hammond HK; Chiamvimonvat N. 2010. Disruption of adenylyl cyclase type V does not rescue the phenotype of cardiac-specific overexpression of Galphaq protein-induced cardiomyopathy. Am J Physiol Heart Circ Physiol 299(5):H1459-67. [PubMed: 20709863] [MGI Ref ID J:166641]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, transgenic mice may be bred to wildtype (noncarrier) mice from the colony or with FVB/NJ inbred mice (Stock No. 001800). Transgenic females develop peripartum cardiomyopathy. Mating System Noncarrier x Hemizygote (Female x Male) 27-JUL-10 Diet Information LabDiet® 5K52/5K67
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $232.00 Female or Male Hemizygous for Tg(Myh6-Gnaq)40Gwd
Price per Pair (US dollars $) Pair Genotype $296.00 Hemizygous for Tg(Myh6-Gnaq)40Gwd x Noncarrier $296.00 Noncarrier x Hemizygous for Tg(Myh6-Gnaq)40Gwd Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
| Pricing for International shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $301.60 Female or Male Hemizygous for Tg(Myh6-Gnaq)40Gwd
Price per Pair (US dollars $) Pair Genotype $384.80 Hemizygous for Tg(Myh6-Gnaq)40Gwd x Noncarrier $384.80 Noncarrier x Hemizygous for Tg(Myh6-Gnaq)40Gwd Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
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|
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Standard Supply
Repository-Live. Repository-Live represents an exclusive set of over 1500 unique mouse models maintained at The Jackson Laboratory to support a vast array of research areas. The breeding colonies for Repository Strains provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. Repository-live orders are treated as custom orders. Within 2 business days, we respond to each availability inquiry or order with various delivery options. Repository Strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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