Overview

These ATPase, Ca++ transporting (Atp2a3 or Serca3) knockout mice exhibit reduced acetylecholine (Ach)-induced aortic relaxation and diminished Ach-responsive Ca2⁺ stores. These mice may be useful for studying endothelial Ca2⁺ signaling and aortic smooth muscle relaxation/contraction.

Donating Investigator

Gary E Shull, University of Cincinnati

Genetic overview

Genetic Background	Generation

Atp2a3^tm1Ges

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Atp2a3	ATPase, Ca++ transporting, ubiquitous

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Research Applications

Cell Biology Research
Cardiovascular Research

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Details

Detailed Description

Homozygotes: A targeting vector was designed to insert a neomycin resistance (neo) cassette into exon 5 of the ATPase, Ca++ transporting, ubiquitous (Atp2a3 or Serca3) gene, abolishing gene function. Serca3 is a Sarco(endo)plasmic reticulum Ca2⁺ ATPase which is expressed in endothelial cells, in epithelial cells of trachea, intestine, and
salivary glands, and in platelets, mast cells, and lymphocytes. In these mice, acetylecholine (Ach)-induced aortic relaxation is reduced, and Ach-responsive Ca2⁺ stores, along with intracellular Ca2⁺ signaling, are diminished. These Serca3^-/-mice do, however, exhibit normal basal blood pressure, glucose tolerance, and insulin secretion. These mice may be useful for studying endothelial Ca2⁺ signaling and aortic smooth muscle relaxation/contraction.

Heterozygote: Heterozygous mice are viable, fertile, and normal in size. They exhibit normal growth, and are phenotypically similar to wildtype mice

Development

A targeting vector was designed to insert a neomycin resistance (neo) cassette into exon 5 of the ATPase, Ca++ transporting, ubiquitous (Atp2a3 or Serca3) gene. The construct was electroporated into 129-derived embryonic stem (ES) cells and correctly targeted ES cells were injected into blastocysts. The resulting chimeric males were bred to Black Swiss females, and these mice were subsequently backcrossed to FVB/N mice for at least 10 generations. Upon arrival at The Jackson Laboratory, mice were bred to FVB/NJ inbred mice for at least one generation to establish the colony.

Control Suggestions

Wild-type from the colony

Approximate Controls

001800 FVB/NJ

Additional Information

Considerations for Choosing Controls

Selected References

Liu LH; Paul RJ; Sutliff RL; Miller ML; Lorenz JN; Pun RY; Duffy JJ; Doetschman T; Kimura Y; MacLennan DH; Hoying JB; Shull GE. 1997. Defective endothelium-dependent relaxation of vascular smooth muscle and endothelial cell Ca2+ signaling in mice lacking sarco(endo)plasmic reticulum Ca2+-ATPase isoform 3. J Biol Chem 272(48):30538-45PubMed: 9374548 MGI: J:44333

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Genetics

Atp2a3^tm1Ges

Allele Symbol: Atp2a3^tm1Ges

Allele Name	targeted mutation 1, Gary E Shull
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	SERCA3^-
Gene Symbol and Name	Atp2a3, ATPase, Ca++ transporting, ubiquitous
Gene Synonym(s)
Strain of Origin	Not Specified
Chromosome	11
Molecular Note	A neomycin resistance gene was inserted into exon 5, which encodes amino acids 109 through 154. Northern blot analysis of RNA isolated from colon, lung, and aorta tissue showed the presence of a shortened transcript in homozygous mutant mice. Sequence analysis of the mutant message identified a cryptic donor site in exon 5 that led to the excision of 84 nucleotides encoding amino acids 127 through 154. Transfection of microsomes, showed that the mutant protein product was incapable of calcium-uptake.
Mutations Made By	Gary Shull, University of Cincinnati

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Cell Biology Research
- Channel and Transporter Defects
  - calcium
Cardiovascular Research
- Vascular Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Atp2a3^tm1Ges/Atp2a3^tm1Ges
involves: Black Swiss

cardiovascular system phenotype

abnormal vascular endothelial cell physiology
- mutant aortic endothelial cells show only a minimal increase in acetylcholine-induced intracellular calcium levels compared to a pronounced increase in wild-type cells and impaired replenishment of the acetylcholine-responsive calcium stores

muscle phenotype

abnormal muscle relaxation
- aortic rings first stimulated to 80-90% of maximum contraction with phenylephrine show reduced relaxation in response to increasing concentrations of acetylcholine (Ach), however both wild-type and mutant aortas fail to respond to Ach when denuded of endothelium, indicating that endothelium-dependent relaxation is reduced in aortas
- thelium, indicating that endothelium-dependent relaxation is reduced in aortas

References

Liu LH; Paul RJ; Sutliff RL; Miller ML; Lorenz JN; Pun RY; Duffy JJ; Doetschman T; Kimura Y; MacLennan DH; Hoying JB; Shull GE. 1997. Defective endothelium-dependent relaxation of vascular smooth muscle and endothelial cell Ca2+ signaling in mice lacking sarco(endo)plasmic reticulum Ca2+-ATPase isoform 3. J Biol Chem 272(48):30538-45PubMed: 9374548 MGI: J:44333

Additional - Atp2a3^tm1Ges related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Atp2a3
- Separated MCA:Atp2a3
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Citation
When using the FVB.Cg-Atp2a3^tm1Ges/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #34260 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

The Jackson Laboratory's Genotype Promise

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.

Terms Of Use

General Terms and Conditions

See MMRRC for Additional Conditions of Distribution

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Atp2a3tm1Ges

Allele Symbol: Atp2a3tm1Ges

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Atp2a3tm1Ges/Atp2a3tm1Gesinvolves: Black Swiss

cardiovascular system phenotype

muscle phenotype

References

Additional - Atp2a3tm1Ges related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Atp2a3^tm1Ges

Allele Symbol: Atp2a3^tm1Ges

Genotype: Atp2a3^tm1Ges/Atp2a3^tm1Ges
involves: Black Swiss

Additional - Atp2a3^tm1Ges related