These inducible PLM S68E transgenic mice express mutant dog Fxyd1 (or phospholemman) under the direction of a modified mouse alpha-myosin heavy chain minimal promoter (Myh6) fused with tetO. Following DOX induction, bitransgenic mice exhibit ventricular arrhythmias and increased mortality (50%) due to heart failure. This strain may be useful for studying phosphlemman as a therapeutic target in ischemic heart disease.
Joseph Y. Cheung, Temple University, School of Medicine
Genetic Background | Generation |
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Allele Type |
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Transgenic (Inducible, Inserted expressed sequence) |
These inducible PLM S68E transgenic mice express mutant dog Fxyd1, FXYD domain-containing ion transport regulator 1 (or phospholemman), under the direction of a modified mouse alpha-myosin heavy chain minimal promoter (Myh6) fused with a tetracycline operator promoter (tetO). Phosphlemman (or FXYD1) is member of the FXYD family of small ion transport regulators. The phosphlemman (or FXYD1) S68E mutation blocks serine phosphorylation and inhibits the ion transporter SLC8A1 (or NCX1), but does not inhibit Na+-K+-ATPase activity.
Mice hemizygous for the transgenic insert are viable and fertile. It is not known if homozygotes are viable.
When mated to mice carrying MHC-tTA (also known as Tg(Myh6-tTA)55Rbns), SLC8A1*S68E expression is directed to cardiac myocytes and regulated with tetracycline or its analog doxycycline (DOX). Following DOX induction, bitransgenic mice exhibit ventricular arrhythmias, bradycardia, increased left ventricular mass, decreased cardiac output, alterations in Ca2+ and Na+ regulation and increased mortality (50%) due to heart failure. This strain may be useful for studying phosphlemman as a therapeutic target in ischemic heart disease.
The inducible PLM S68E transgene was designed with 279 bp of the mutant dog Fxyd1 gene (harboring an amino acid substitution of serine to glutamic acid at codon 68) plus the 5’ and 3’ untranslated sequences driven by a modified mouse alpha-myosin heavy chain minimal promoter (Myh6) fused with tetracycline responsive element (TRE or tetO). The transgene was injected into fertilized FVB/N mouse eggs. Founder line 39 was subsequently established and bred to FVB/NJ for several generations. Upon arrival at The Jackson Laboratory Repository, the mice were bred with FVB/NJ mice for at least one generation to establish the colony.
Expressed Gene | FXYD1, FXYD domain containing ion transport regulator 1, dog, domestic |
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Site of Expression | When mated to mice carrying MHC-tTA (also known as Tg(Myh6-tTA)55Rbns), SLC8A1*S68E expression is directed to cardiac myocytes and regulated with tetracycline or its analog doxycycline |
Allele Name | transgene insertion 39, Joseph Y Cheung |
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Allele Type | Transgenic (Inducible, Inserted expressed sequence) |
Allele Synonym(s) | PLM S68E TG |
Gene Symbol and Name | Tg(Myh6*/tetO-FXYD1*S68E)39Jych, transgene insertion 39, Joseph Y Cheung |
Gene Synonym(s) | |
Promoter | Myh6, myosin, heavy polypeptide 6, cardiac muscle, alpha, murine, murine |
Promoter | tetO, tet operator, |
Expressed Gene | FXYD1, FXYD domain containing ion transport regulator 1, dog, domestic |
Site of Expression | When mated to mice carrying MHC-tTA (also known as Tg(Myh6-tTA)55Rbns), SLC8A1*S68E expression is directed to cardiac myocytes and regulated with tetracycline or its analog doxycycline |
Strain of Origin | FVB/N |
Chromosome | UN |
Molecular Note | This transgene was designed with 279 bp of the mutant dog Fxyd1 gene (harboring an amino acid substitution of serine to glutamic acid at codon 68) plus the 5' and 3' untranslated sequences driven by a modified mouse alpha-myosin heavy chain minimal promoter (Myh6) fused with tetracycline responsive element (TRE or tetO). Founder line 39 was characterized. |
While maintaining a live colony, these mice are bred as hemizygotes. The donating investigator has not attempted to generate homozygous mice.
When using the PLM S68E TG mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #41837 in your Materials and Methods section.
Facility Barrier Level Descriptions
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.
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