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.
John R Dedman, University of Cincinnati College of Med.
Genetic Background | Generation |
---|---|
|
Allele Type |
---|
Transgenic (Inserted expressed sequence) |
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.
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.
Expressed Gene | Pln, phospholamban, mouse, laboratory |
---|---|
Expressed Gene | Camk2a, calcium/calmodulin-dependent protein kinase II alpha, mouse, laboratory |
Site of Expression |
Allele Name | transgene insertion 46, John R Dedman |
---|---|
Allele Type | Transgenic (Inserted expressed sequence) |
Allele Synonym(s) | alpha-MHC-AIP4-SR; SR-AIP |
Gene Symbol and Name | Tg(Myh6-AIP/PLN*)46Jded, transgene insertion 46, John R Dedman |
Gene Synonym(s) | |
Promoter | Myh6, myosin, heavy polypeptide 6, cardiac muscle, alpha, murine, murine |
Expressed Gene | Pln, phospholamban, mouse, laboratory |
Expressed Gene | Camk2a, calcium/calmodulin-dependent protein kinase II alpha, mouse, laboratory |
Strain of Origin | FVB/N |
Chromosome | UN |
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). |
Mutations Made By | John Dedman, University of Cincinnati College of Med. |
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.
When using the FVB/N-Tg(Myh6-AIP/PLN*)46Jded/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #008716 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Hemizygous for Tg(Myh6-AIP/PLN*)46Jded |
Frozen Mouse Embryo | FVB/N-Tg(Myh6-AIP/PLN*)46Jded/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | FVB/N-Tg(Myh6-AIP/PLN*)46Jded/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | FVB/N-Tg(Myh6-AIP/PLN*)46Jded/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | FVB/N-Tg(Myh6-AIP/PLN*)46Jded/J Frozen Embryo | $3373.50 |
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
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.