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| SR-AIP transgenic mice carry the α-MHC-AIP4-SR transgene, with expression of AIP4 (a tetramer of the CaMKII autocamtide inhibitory peptide AIP) directed to the sarcoplasmic reticulum (SR) of the heart by the murine alpha-myosin heavy chain (α-MHC or Myh6) promoter and a truncated phospholamban (PLB) transmembrane domain (harboring two loss-of-function mutations to prevent direct SERCA inhibition by the fusion protein). The SR-targeted AIP concatemer peptide binds CaMKII, preventing phosphorylation of PLB and subsequent activation of SERCA, thereby increasing diastolic intracellular calcium. These SR-AIP transgenic mice may be useful in studying sarcoplasmic reticulum-targeted CaMKII inhibition, cardiac disease, and the effects of pregnancy upon heart function. | |||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Strain Information
Type Coisogenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Donating Investigator John R Dedman, University of Cincinnati College of Med. Description
SR-AIP transgenic mice carry the α-MHC-AIP4-SR transgene. Hemizygous SR-AIP mice are viable and fertile, with expression of AIP4 (a tetramer of the CaMKII autocamtide inhibitory peptide AIP) directed to the sarcoplasmic reticulum (SR) of the heart by the murine alpha-myosin heavy chain (α-MHC or Myh6) promoter and a truncated phospholamban (PLB) transmembrane domain (harboring two loss-of-function mutations to prevent direct SERCA inhibition by the fusion protein). FLAG epitope expression may be used to identify presence of the fusion protein. The SR-targeted AIP concatemer peptide binds CaMKII, preventing phosphorylation of PLB and subsequent activation of SERCA, thereby increasing diastolic intracellular calcium. Whole heart function and diastolic relaxation are slightly impaired, and pregnancy leads to earlier onset of cardiac hypertrophy. These SR-AIP transgenic mice may be useful in studying sarcoplasmic reticulum-targeted CaMKII inhibition and cardiac disease, as well as the effects of pregnancy upon heart function.Development
The α-MHC-AIP4-SR transgene was designed with the 5.5-kb murine alpha-myosin heavy chain (α-MHC or Myh6) promoter, an AIP4 CaMKII inhibitor domain (encoding a tetramer of the CaMKII autocamtide inhibitory peptide AIP (KKALRRQEAVDAL; a 13-amino acid sequence known to be a highly specific and potent inhibitor of CaMKII)), a FLAG epitope (DYKDDDDK), and a synthetic truncated phospholamban (PLB) transmembrane domain (amino acids 23-52 with L31A/N34A mutations to ensure AIP4 is targeted to the sarcoplasmic reticulum (SR) without the usual inhibition of the PLB transmembrane domain on SERCA activity). This transgene was injected into pronuclei of FVB/N fertilized mouse oocytes, and transgenic offspring were bred to FVB/N to establish founder line 46 (found to carry an estimated 2 copies of the transgene). These SR-AIP transgenic mice were then bred together for approximately 18-20 generations prior to arrival at The Jackson Laboratory. Upon arrival, SR-AIP mice were bred with FVB/NJ inbred mice (Stock No. 001800) to establish the colony.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
Related Strains
Strains carrying other alleles of Camk2a
016198 129S6.Cg-Tg(Camk2a-tTA)1Mmay/JlwsJ 002362 B6.129P2-Camk2atm1Sva/J 007574 B6.Cg-Tg(Camk2a-Crebbp*)1364Tabe/J 005855 B6.Cg-Tg(Camk2a-Prkaca)426Tabe/J 005359 B6.Cg-Tg(Camk2a-cre)T29-1Stl/J 007004 B6.Cg-Tg(Camk2a-tTA)1Mmay/DboJ 012362 B6;129S6-Tg(Camk2a-cre/ERT2)1Aibs/J 003010 B6;CBA-Tg(Camk2a-tTA)1Mmay/J 004995 C3H-Tg(Camk2a-Creb1/ESR1)3Sva/J 006575 C57BL/6-Camk2atm1Vyb/J 013760 C57BL/6-Tg(Camk2a-AIDPak)21Stl/J 006579 C57BL/6-Tg(Camk2a-Bdnf)A9Stl/J 008088 C57BL/6-Tg(Camk2a-ESR1/Disc1*)2698.1Sva/J 005087 C57BL/6-Tg(Camk2a-IDE)1Selk/J 005086 C57BL/6-Tg(Camk2a-MME)3Selk/J 008833 C57BL/6-Tg(Camk2a-UBB)3413-1Fwvl/J 010712 C57BL/6-Tg(Camk2a-tTA)1Stl/J View Strains carrying other alleles of Camk2a (17 strains)
Phenotype
Phenotype Information
- Potential model based on transgenic expression of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested. Cardiomyopathy, Dilated, 1p; CMD1P (PLN)
Cardiomyopathy, Familial Hypertrophic, 18; CMH18 (PLN)
assigned by genotype
Tg(Myh6-AIP/PLN*)46Jded/0
FVB/N-Tg(Myh6-AIP/PLN*)46Jded
- cardiovascular system phenotype
- abnormal cardiac muscle relaxation
- cardiac relaxation is 26% slower in transgenic mice (MGI Ref ID J:84333)
- abnormal heart atrium morphology
- enlarged heart left atrium
- observed in 7 month old females that have produced at least three litters (MGI Ref ID J:84333)
- abnormal heart ventricle morphology
- myocyte hypertrophy is observed in 7 month old females that have produced at least three litters (MGI Ref ID J:84333)
- increased heart left ventricle size
- observed in 7 month old females that have produced at least three litters (MGI Ref ID J:84333)
- cardiac fibrosis
- observed in left atrium and ventricle of 7 month old females that have produced at least three litters (MGI Ref ID J:84333)
- cardiac hypertrophy
- although not observed in 3-4 month old mice, hypertrophy is found in 7 month old females that have produced at least three litters (MGI Ref ID J:84333)
- congestive heart failure
- dilated heart failure is observed in 7 month old females that have produced at least three litters and in 12-14 month old males (MGI Ref ID J:84333)
- decreased heart rate
- mice exhibit a decreased heart rate under basal and stimulated conditions (MGI Ref ID J:84333)
- increased heart rate
- maximal heart response is increased in response to dobutamine as compared to control (MGI Ref ID J:84333)
- increased heart weight
- 2.82-fold increase observed in 7 month old females that have produced at least three litters (MGI Ref ID J:84333)
- increased left ventricle diastolic pressure
- left ventricle end diastolic pressure (LVEDP) is higher in transgenic mice (MGI Ref ID J:84333)
- increased left ventricle systolic pressure (MGI Ref ID J:84333)
- muscle phenotype
- abnormal cardiac muscle relaxation
- cardiac relaxation is 26% slower in transgenic mice (MGI Ref ID J:84333)
- respiratory system phenotype
- increased lung weight
- 2.87-fold increase observed in 7 month old females that have produced at least three litters (MGI Ref ID J:84333)
This mouse can be used to support research in many areas including:
Cardiovascular Research
Heart Abnormalities
Other
Cell Biology Research
Channel and Transporter Defects
calcium
Developmental Biology Research
Internal/Organ Defects
heart
Internal/Organ Research
Heart Abnormalities
Research Tools
Cardiovascular Research
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Tg(Myh6-AIP/PLN*)46Jded | ||
|---|---|---|---|
| Allele Name | transgene insertion 46, John R Dedman | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | SR-AIP; alpha-MHC-AIP4-SR; | ||
| Mutation Made By | John Dedman, University of Cincinnati College of Med. | ||
| Strain of Origin | FVB/N | ||
| Expressed Gene | Pln, phospholamban, mouse, laboratory | ||
| Expressed Gene | Camk2a, calcium/calmodulin-dependent protein kinase II alpha, mouse, laboratory | ||
| Promoter | Myh6, myosin, heavy polypeptide 6, cardiac muscle, alpha, murine, murine | ||
| Molecular Note | The alpha-MHC-AIP4-SR transgene was designed with the 5.5-kb murine alpha-myosin heavy chain (alpha-MHC or Myh6) promoter, an AIP4 CaMKII inhibitor domain (encoding a tetramer of the CaMKII autocamtide inhibitory peptide AIP (KKALRRQEAVDAL; a 13-amino acid sequence known to be a highly specific and potent inhibitor of CaMKII)), a FLAG epitope (DYKDDDDK), and a synthetic truncated phospholamban (PLB) transmembrane domain (amino acids 23-52 with L31A/N34A mutations to ensure AIP4 is targeted to the sarcoplasmic reticulum (SR) without the usual inhibition of the PLB transmembrane domain on SERCA activity). This transgene was injected into pronuclei of FVB/N fertilized mouse oocytes, and transgenic offspring were bred to FVB/N to establish founder line 46 (found to carry an estimated 2 copies of the transgene). [MGI Ref ID J:84333] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(Myh6-AlP/PLN*)46Jded, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Chun SJ; Rasband MN; Sidman RL; Habib AA; Vartanian T. 2003. Integrin-linked kinase is required for laminin-2-induced oligodendrocyte cell spreading and CNS myelination. J Cell Biol 163(2):397-408. [PubMed: 14581460] [MGI Ref ID J:86333]
Additional References
Tg(Myh6-AIP/PLN*)46Jded relatedJi Y; Li B; Reed TD; Lorenz JN; Kaetzel MA; Dedman JR. 2003. Targeted inhibition of Ca2+/calmodulin-dependent protein kinase II in cardiac longitudinal sarcoplasmic reticulum results in decreased phospholamban phosphorylation at threonine 17. J Biol Chem 278(27):25063-71. [PubMed: 12692124] [MGI Ref ID J:84333]
Picht E; DeSantiago J; Huke S; Kaetzel MA; Dedman JR; Bers DM. 2007. CaMKII inhibition targeted to the sarcoplasmic reticulum inhibits frequency-dependent acceleration of relaxation and Ca2+ current facilitation. J Mol Cell Cardiol 42(1):196-205. [PubMed: 17052727] [MGI Ref ID J:128032]
Health & husbandry
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Health & Colony Maintenance Information
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.Colony Maintenance
Breeding & Husbandry When maintaining a live colony, hemizygous mice may be bred to wildtype (noncarrier) siblings or to FVB/NJ inbred mice (Stock No. 001800). As pregnancy exacerbates earlier onset of cardiac hypertrophy, transgenic female health should be observed during pregnancy. The donating investigator claims to breed homozygous mice together.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2085.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2710.50 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
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Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
General Supply Notes
- Genomic DNA is available for this strain from the Mouse DNA Resource.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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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 Information
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