Strain Name:
FVB/N-Tg(Myh6*/tetO-FXYD1*S68E)39Jych/Mmjax
Stock Number:
041837-JAX
Citation ID:
RRID:MMRRC_041837-JAX
Other Names:
Tg MHC PLMS68E

Strain Information

Myh6
Name: myosin, heavy polypeptide 6, cardiac muscle, alpha
Synonyms: Myhc-a, alpha cardiac MHC, Myhca, alphaMHC, alpha myosin, A830009F23Rik, cardiomyopathy, hypertrophic 1, alpha-MHC
Type: Gene
Species: Mouse
Chromosome: 14
NCBI: 17888
HGNC: HGNC:7576
Homologene: 124414
Fxyd1
Name: FXYD domain-containing ion transport regulator 1
Synonyms: PLM, PML, 1110006M24Rik, phospholemman, 0610012C17Rik
Type: Gene
Species: Mouse
Chromosome: 7
NCBI: 56188
HGNC: HGNC:4025
Homologene: 3691
Tg(Myh6-Fxyd1)39Jych
Name:
Type: Transgene
Species: Mus musculus (mouse)
Chromosome:
Genetic Alterations
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.
ES Cell Line
NA
Phenotype
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.
MeSH Terms
  • Action Potentials/genetics
  • Action Potentials/physiology
  • Animals
  • Arrhythmias, Cardiac/genetics
  • Arrhythmias, Cardiac/metabolism
  • Arrhythmias, Cardiac/physiopathology
  • Bradycardia/genetics
  • Bradycardia/metabolism
  • Bradycardia/mortality
  • Calcium/metabolism
  • Calcium Channels, L-Type/physiology
  • Female
  • Gene Expression/physiology
  • Heart Failure/genetics
  • Heart Failure/metabolism
  • Heart Failure/mortality
  • Male
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism
  • Mice
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Myocardial Contraction/physiology
  • Myocytes, Cardiac/cytology
  • Myocytes, Cardiac/physiology
  • Phosphoproteins/genetics
  • Phosphoproteins/metabolism
  • Potassium/metabolism
  • Receptors, Adrenergic, beta/metabolism
  • Sodium/metabolism
  • Sodium-Calcium Exchanger/genetics
  • Sodium-Calcium Exchanger/metabolism
  • Adrenergic beta-Agonists/pharmacology
  • Calcium Channels, L-Type/metabolism
  • Calcium Signaling
  • Cardiotonic Agents/pharmacology
  • Disease Models, Animal
  • Mutation
  • Myocardial Contraction/drug effects
  • Myocardial Infarction/drug therapy
  • Myocardial Infarction/metabolism
  • Myocardial Infarction/pathology
  • Myocardial Infarction/physiopathology
  • Myocardial Reperfusion Injury/drug therapy
  • Myocardial Reperfusion Injury/metabolism
  • Myocardial Reperfusion Injury/pathology
  • Myocardial Reperfusion Injury/physiopathology
  • Recovery of Function
  • Ryanodine Receptor Calcium Release Channel/metabolism
  • Sarcoplasmic Reticulum/metabolism
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism
  • Sodium-Potassium-Exchanging ATPase/metabolism
  • Stroke Volume
  • Up-Regulation
  • Ventricular Dysfunction, Left/metabolism
  • Ventricular Dysfunction, Left/pathology
  • Ventricular Dysfunction, Left/physiopathology
  • Ventricular Dysfunction, Left/prevention & control
  • Ventricular Function, Left/drug effects
  • Ventricular Pressure
Strain Development
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 MMRRC, the mice were bred with FVB/NJ mice for at least one generation to establish the colony.
Suggested Control Mice
Wild-type littermates
MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact csmmrrc@jax.org. Older strains may not have this information.
  • Cardiovascular
Donor
Joseph Cheung, M.D., Ph.D., Temple University School of Medicine.
Primary Reference

Song J, Gao E, Wang J, Zhang XQ, Chan TO, Koch WJ, Shang X, Joseph JI, Peterson BZ, Feldman AM, Cheung JY. Constitutive overexpression of phosphomimetic phospholemman S68E mutant results in arrhythmias, early mortality, and heart failure: potential involvement of NCX1. Am J Physiol Heart Circ Physiol. 2012 Feb 1;302(3):H770-81. Epub 2011 Nov 11. (Medline PMID: 22081699)

Wang J, Song J, Gao E, Zhang XQ, Gu T, Yu D, Koch WJ, Feldman AM, Cheung JY. Induced overexpression of phospholemman S68E mutant improves cardiac contractility and mortality after ischemia-reperfusion. Am J Physiol Heart Circ Physiol. 2014 Apr 1;306(7):H1066-77. Epub 2014 Jan 31. (Medline PMID: 24486513)

Colony and Husbandry Information

Cryo-recovered strains distributed by the MMRRC at JAX are shipped to the customer from the Pathogen & Opportunistic-Free Animal Room G200 - see https://www.jax.org/jax-mice-and-services/customer-support/customer-service/animal-health/health-status-reports.

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email csmmrrc@jax.org.
Coat Color
white
MMRRC Breeding System
Outcross to non-inbred (hybrid or outbred) mate
Overall Breeding Performance
Good
NOTE: "Hemizygote" as used here refers to males carrying a mutation on the X Chromosome or mice of either sex carrying an inserted transgene with no homologous allele on the other chromosome.
Viability and Fertility: Female Male Comments
Homozygotes are viable: Undetermined Undetermined
Homozygotes are fertile: Unknown Unknown
Hetero/Hemizygotes are fertile: Yes Yes
Age Reproductive Decline: >12 months >12 months
Average litter size
5-9
Recommended wean age
3 weeks

Order Request Information

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

The donor or their institution limits the distribution to non-profit institutions only.

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*
Units Notes
041837-JAX-SPERM Cryo-preserved spermatozoa $437.00 / Non-Profit Aliquot Approximate quantity3
041837-JAX-RESUS Litter recovered from cryo-archive $2,022.00 / Non-Profit Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.