Strain Name:
B6J(Cg)-Tg(tetO/CMV-ATP2B4,-lacZ)1Husa Tg(Myh6-tTA)6Smbf/Mmjax
Stock Number:
043951-JAX
Citation ID:
RRID:MMRRC_043951-JAX
Other Names:
huPMCA4b Tet-Off, Human PMCA4b Tet-Off Overexpresser

Strain Information

Tg(Myh6-tTA)6Smbf
Name: transgene insertion 6, Section of Myocardial Biology - Fishman Lab
Synonyms: 2.9alphatTA, alphaMHC-tTA, alphaMtTA, Tg(MHCAtTA)6Smbf
Type: Allele
Species: Multi-species
Chromosome: random insertion
Alteration at locus: Transgenic (random, gene disruption)
Tg(tetO/CMV-ATP2B4,-lacZ)1Husa
Name: transgene insertion 1, Mansoor Husain
Synonyms: hPMCA4b
Type: Allele
Species: Multi-species
Chromosome: random insertion
Alteration at locus: Transgenic (random, gene disruption)
tTA
Name: tetracycline-controlled transactivator protein
Type: Gene
Species: Multi-species
Chromosome:
Alteration at locus: Transgenic (random, gene disruption)
lacZ
Name: beta galactosidase
Type: Gene
Species: Escherichia coli (bacterium)
Chromosome:
Alteration at locus: Transgenic (random, gene disruption)
Myh6
Name: myosin, heavy polypeptide 6, cardiac muscle, alpha
Type: Gene
Species: Rattus norvegicus (norway rat)
Chromosome: 15
Alteration at locus: Transgenic (random, gene disruption)
ATP2B4
Name: ATPase plasma membrane Ca2+ transporting 4
Type: Gene
Species: Homo sapiens (human)
Chromosome: 1
Alteration at locus: Transgenic (random, gene disruption)
CMV
Name: cytomegalovirus
Type: Regulatory Region
Species: Virus
Chromosome:
Alteration at locus: Transgenic (random, gene disruption)
tetO
Name: tetracycline-responsive promoter element
Type: Regulatory Region
Species: Multi-species
Chromosome:
Alteration at locus: Transgenic (random, gene disruption)
Genetic Alterations

Random insertion of a transgene bearing a the bi-directional, Tet-sensitive pBi-1 (PMID:7567477) with LacZ on one end and human ATP2B4 on the other end. Another random insertion has the rat myosin, heavy polypeptide 6, cardiac muscle, alpha (Myh6) promoter driving Tet Transactivator cDNA (tTa) expression.

Phenotype

Homozygous: N/A

Hetero/Hemizygous: Total cardiac NOS and nNOS-specific activities were reduced in mice with cardiac overexpression of hPMCA4b while nNOS, eNOS and iNOS protein levels did not differ. hMPCA4b-overexpressing mice also exhibited elevated systolic blood pressure vs. controls, with increased contractility and lusitropy in vivo. In isolated hearts undergoing IRI, hPMCA4b over-expression was cardioprotective. NO donor-treated hearts overexpressing hPMCA4b showed reduced LVDP and larger infarct size versus vehicle-treated hearts undergoing IRI, demonstrating that the cardioprotective benefits of hPMCA4b-repressed nNOS are lost by restoring NO availability. Finally, both pre-existing and post-MI induction of hPMCA4b overexpression reduced infarct expansion and improved survival from HF. Binary transgenic (BT: tTA+/hPMCA4b+) mice were born at expected frequencies (25% from heterozygous crosses), were viable and showed normal development to over 2 years of age. X-gal staining and immunohistochemistry revealed nuclear-localized β-galactosidase in the mouse cardiomyocytes.

MeSH Terms
  • Animals
  • Aorta/enzymology
  • Arginine/analogs & derivatives
  • Arginine/pharmacology
  • Blood Pressure/drug effects
  • Blood Pressure/physiology
  • Calcium/metabolism
  • Calcium-Transporting ATPases/genetics
  • Calcium-Transporting ATPases/metabolism
  • Cation Transport Proteins
  • Cell Line
  • Cells, Cultured
  • Cyclic GMP/metabolism
  • Dose-Response Relationship, Drug
  • Doxycycline/pharmacology
  • Enzyme Inhibitors/pharmacology
  • Female
  • Gene Expression Regulation, Enzymologic/drug effects
  • Genotype
  • Humans
  • In Vitro Techniques
  • Isoenzymes/genetics
  • Isoenzymes/metabolism
  • Male
  • Mesenteric Arteries/drug effects
  • Mesenteric Arteries/physiology
  • Mice
  • Mice, Transgenic
  • Muscle, Smooth, Vascular/cytology
  • Muscle, Smooth, Vascular/enzymology
  • Muscle, Smooth, Vascular/metabolism
  • NG-Nitroarginine Methyl Ester/pharmacology
  • Nitric Oxide Synthase/antagonists & inhibitors
  • Nitric Oxide Synthase Type I
  • Phenylephrine/pharmacology
  • Plasma Membrane Calcium-Transporting ATPases
  • Potassium Chloride/pharmacology
  • Vasoconstriction/drug effects
  • Vasomotor System/drug effects
  • Vasomotor System/physiology
  • Gene Expression Regulation
  • Heart/physiology
  • Lac Operon
  • Organ Specificity
  • Promoter Regions, Genetic
  • Rats
  • Tetracycline/metabolism
  • Transgenes
Strain Development
Generation of doxycycline-regulated (Tet-Off) human PMCA4b-expressing transgenic mice involved mating huPMCA4b mice with α-MHC-tTA mice generously provided by Dr. Glenn Fishman. Crosses generated binary transgenic (BT: tTA+/hPMCA4b+)
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
  • Models for Human Disease
  • Research Tools
Donor
Mansoor Husain, Toronto General Hospital Research Institute.
Glenn I. Fishman, M.D., NYU School of Medicine.
Primary Reference

Sadi AM, Afroze T, Siraj MA, Momen A, White-Dzuro C, Zarrin-Khat D, Handa S,Ban K, Kabir MG, Trivieri MG, Gros R, Backx P, Husain M. Cardiac-specificinducible overexpression of human plasma membrane Ca(2+) ATPase 4b iscardioprotective and improves survival in mice following ischemic injury. ClinSci (Lond). 2018 Mar 26;132(6):641-654. doi: 10.1042/CS20171337. Print 2018 Mar30. (Medline PMID: 29487197)

Gros R, Afroze T, You XM, Kabir G, Van Wert R, Kalair W, Hoque AE, Mungrue IN,Husain M. Plasma membrane calcium ATPase overexpression in arterial smooth muscleincreases vasomotor responsiveness and blood pressure. Circ Res. 2003 Oct3;93(7):614-21. Epub 2003 Aug 21. (Medline PMID: 12933703)

Yu Z, Redfern CS, Fishman GI. Conditional transgene expression in the heart.Circ Res. 1996 Oct;79(4):691-7. (Medline PMID: 8831492)

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
Black
Eye
Black
MMRRC Breeding System
Sib-mating
Breeding Scheme(s)
Binary Transgenic mice (BT mice) with the genotype tTA+/hPMCA4b+ were mated with each other. Crosses generated binary transgenic (BT: tTA+/hPMCA4b+) and non-binary transgenic (NBT: tTA+/hPMCA4b− or tTA−/hPMCA4b+) littermates.
Generation
N10+ (C57BL/6J)
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: Undetermined Undetermined
Hetero/Hemizygotes are fertile: Yes Yes
Age Reproductive Decline: Greater than 12 months Greater than 12 months
Bred to Homozygosity
No
Average litter size
4-6
Recommended wean age
3 weeks
Average Pups Weaned
4-6

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.

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

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.

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
043951-JAX-EMBRYO Cryo-preserved embryos $1,038.00 / Non-Profit Aliquot Approximate quantity2 : 20-40 embryos / aliquot
043951-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.