Strain Name:
FVB.129X1(Cg)-Atp2a2tm1Ges/Mmjax
Stock Number:
036806-JAX
Citation ID:
RRID:MMRRC_036806-JAX
Other Names:
Atp2a2, SERCA2; sarco(endo)plasmic reticulum Ca-ATPase isoform 2; the cardiac SR Ca pump; the ubiquitous endoplasmic reticulum Ca pump

Gene Information

Atp2a2tm1Ges
Name: ATPase, Ca++ transporting, cardiac muscle, slow twitch 2; targeted mutation 1, Gary E Shull
Synonyms: SERCA2a knockout, SERCA2a-
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 5
Alteration at locus: Knockout
Atp2a2
Name: ATPase, Ca++ transporting, cardiac muscle, slow twitch 2
Synonyms: sarco/endoplasmic reticulum Ca2+-ATPase 2, SERCA2, 9530097L16Rik, D5Wsu150e, SERCA2B, Serca2a
Type: Gene
Species: Mus musculus (mouse)
Chromosome: 5
Alteration at locus: Knockout
NCBI: 11938
HGNC: HGNC:812
Homologene: 80167
Genetic Alterations

A genomic clone containing the 59 end of the mouse Atp2a2 gene was isolated from a strain 129/SvJ phage library and used to prepare targeting constructs. A neo cassette replaced part of the promoter region and first exon in the Atp2a2 gene, thereby eliminating expression of the transcript.

Genotype Determination
ES Cell Line
Not specified
Phenotype

Homozygous: Embryonic lethal 

Heterozygous: Heterozygotes exhibit a reduction in cardiac contractility (SERCA2 is the cardiac SR Ca pump), susceptibility to cardiac disease in response to pressure overload, and a reduced force-frequency response in heart; the most dramatic phenotype is a high incidence of squamous cell tumors of keratinized epithelial tissues (approximately 90%). In humans, SERCA2 heterozygosity causes Darier Disease, a skin condition involving keratinocytes.

Mammalian Phenotype Terms
Allelic Composition: Atp2a2tm1Ges/Atp2a2tm1Ges (Genetic Background: involves: 129X1/SvJ * Black Swiss )

Allelic Composition: Atp2a2tm1Ges/Atp2a2+ (Genetic Background: involves: 129X1/SvJ )

Allelic Composition: Atp2a2tm1Ges/Atp2a2+ (Genetic Background: involves: 129X1/SvJ * Black Swiss )

MeSH Terms
  • Animals
  • Base Sequence
  • Calcium/metabolism
  • Calcium-Transporting ATPases/genetics
  • Calcium-Transporting ATPases/metabolism
  • DNA Primers
  • Female
  • Heart/physiopathology
  • Heterozygote
  • Isoenzymes/genetics
  • Isoenzymes/metabolism
  • Male
  • Mice
  • Mice, Mutant Strains
  • Mutation
  • Phenotype
  • RNA, Messenger/genetics
  • Sarcoplasmic Reticulum/enzymology
  • Alleles
  • Carcinoma, Squamous Cell/enzymology
  • Carcinoma, Squamous Cell/genetics
  • Genes, p53
  • Genes, ras
  • Genetic Predisposition to Disease
  • Humans
  • Keratinocytes/metabolism
  • Keratins/metabolism
  • Loss of Heterozygosity
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Stomach Neoplasms/enzymology
  • Stomach Neoplasms/genetics
  • Tumor Suppressor Protein p53/biosynthesis
  • Tumor Suppressor Protein p53/genetics
  • Papilloma/enzymology
  • Papilloma/genetics
  • Cardiac Catheterization
  • Diastole
  • Echocardiography
  • Heart Failure/diagnostic imaging
  • Heart Failure/metabolism
  • Heart Failure/physiopathology
  • Hypertrophy, Left Ventricular/diagnostic imaging
  • Hypertrophy, Left Ventricular/metabolism
  • Hypertrophy, Left Ventricular/physiopathology
  • Mice, Knockout
  • Systole
  • Cardiac Output, Low/metabolism
  • Cardiac Output, Low/physiopathology
  • Mice, Transgenic
  • Models, Animal
  • Myocardial Contraction
  • Myocardium/chemistry
  • Myocardium/metabolism
  • Norepinephrine/analysis
  • Norepinephrine/blood
  • Perfusion
  • Sarcoplasmic Reticulum/metabolism
  • Brain/enzymology
  • Calcium Signaling/physiology
  • Calcium-Transporting ATPases/deficiency
  • Carbachol/pharmacology
  • Cell Membrane Permeability
  • Darier Disease/genetics
  • Exocytosis/physiology
  • Gene Expression Regulation, Enzymologic/drug effects
  • In Vitro Techniques
  • Large-Conductance Calcium-Activated Potassium Channels
  • Pancreas/enzymology
  • Pancreas/physiology
  • Potassium Channels/physiology
  • Potassium Channels, Calcium-Activated
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription, Genetic/drug effects
Strain Development

The clone containing the Atp2a2 gene was isolated from a strain 129/SvJ phage library. Target vector was transfected by electroportation into ES cells derived from 129X1/SvJ. The selected ES cell lines containing the disrupted Atp2a2 gene were used for blastocyst-mediated transgenesis. The resulting chimeric mice were mated to Black Swiss mice and backcrossed to the FVB/N mice.

Suggested Control Mice
Wild-type littermates or FVB/N
  • Apoptosis
  • Cancer
  • Cardiovascular
  • Cell Biology
  • Dermatology
  • Diabetes/Obesity
  • Models for Human Disease
    • Darier Disease, a skin condition involving keratinocytes
Donor
Gary Shull, Ph.D., University of Cincinnati College of Medicine.
Primary Reference

Periasamy M, Reed TD, Liu LH, Ji Y, Loukianov E, Paul RJ, Nieman ML, Riddle T, Duffy JJ, Doetschman T, Lorenz JN, Shull GE. Impaired cardiac performance in heterozygous mice with a null mutation in the sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 (SERCA2) gene. J Biol Chem. 1999 Jan 22; 274(4): 2556-62. (Medline PMID: 9891028)

Prasad V, Boivin GP, Miller ML, Liu LH, Erwin CR, Warner BW, Shull GE. Haploinsufficiency of Atp2a2, encoding the sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 Ca2+ pump, predisposes mice to squamous cell tumors via a novel mode of cancer susceptibility. Cancer Res. 2005 Oct 1;65(19):8655-61. (Medline PMID: 16204033)

Liu LH, Boivin GP, Prasad V, Periasamy M, Shull GE. Squamous cell tumors in mice heterozygous for a null allele of Atp2a2, encoding the sarco(endo)plasmic reticulum Ca2+-ATPase isoform 2 Ca2+ pump. J Biol Chem. 2001 Jul 20; 276(29): 26737-40. (Medline PMID: 11389134)

Schultz Jel J, Glascock BJ, Witt SA, Nieman ML, Nattamai KJ, Liu LH, Lorenz JN, Shull GE, Kimball TR, Periasamy M. Accelerated onset of heart failure in mice during pressure overload with chronically decreased SERCA2 calcium pump activity. Am J Physiol Heart Circ Physiol. 2004 Mar;286(3):H1146-53. (Medline PMID: 14630633)

Huke S, Liu LH, Biniakiewicz D, Abraham WT, Periasamy M. Altered force-frequency response in non-failing hearts with decreased SERCA pump-level. Cardiovasc Res. 2003 Sep 1;59(3):668-77. (Medline PMID: 14499868)

Zhao XS, Shin DM, Liu LH, Shull GE, Muallem S. Plasticity and adaptation of Ca2+ signaling and Ca2+-dependent exocytosis in SERCA2(+/-) mice. EMBO J. 2001 Jun 1;20(11):2680-9. (Medline PMID: 11387203)

Colony and Husbandry Information

No special requirements. Heterozygotes appear healthy until tumors and cardiac phenotypes develop.
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
Backcross
Breeding Scheme(s)

Wild-type (FVB/N) female x Heterozygous male or reciprocal mating.

Generation
N10+
Overall Breeding Performance
Excellent
Viability and Fertility: Female Male Comments
Homozygotes are viable: No No
Homozygotes are fertile: N/A N/A
Heterozygotes are fertile: Yes Yes Develop cancer and cardiac phenotypes.
Age Reproductive Decline: Not specified Not specified
Average litter size
Not specified
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
036806-JAX-SPERM Cryo-preserved spermatozoa $437.00 / Non-Profit Aliquot Approximate quantity3
036806-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.