Overview

Also Known As:FVB.Cg-Atp2b4^tm1Ges/Mmjax

Mice homozygous for a null Atp2b4 or PMCA4 (Ca++ transporting ATPase, plasma membrane 4) allele exhibit male infertility (due to loss of hyperactivate sperm motility), increased apoptosis in portal vein smooth muscle cells, accelerated osteoclastogenesis, osteopenia, attenuated Ca signaling in B lymphocytes,and increased cardiac hypertrophy following pressure overload stimulation. This strain may be useful for studying calcium signaling in male infertility, lymphocytes, osteoclasts and smooth muscle contractility.

Donating Investigator

Gary E Shull, University of Cincinnati

Genetic overview

Genetic Background	Generation

Atp2b4^tm1Ges

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Atp2b4	ATPase, Ca++ transporting, plasma membrane 4

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Research Applications

Cardiovascular Research
Cell Biology Research
Immunology, Inflammation and Autoimmunity Research
Reproductive Biology Research
Internal/Organ Research

View All Research Applications

Details

Development

A targeting vector containing the neomycin resistance gene was used to replace codons 448-474 in exon 11, a region encoding the catalytic phosphorylation site. The construct was electroporated into 129-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to Black Swiss mice. Mice from the colony were then backcrossed to FVB/N for at least 10 generations. Upon arrival, mice were bred to FVB/NJ for at least 1 generation to establish the colony.

Control Suggestions

001800 FVB/NJ

Additional Information

Considerations for Choosing Controls

Selected References

Okunade GW; Miller ML; Pyne GJ; Sutliff RL; O'Connor KT; Neumann JC; Andringa A; Miller DA; Prasad V; Doetschman T; Paul RJ; Shull GE. 2004. Targeted ablation of plasma membrane Ca2+-ATPase (PMCA) 1 and 4 indicates a major housekeeping function for PMCA1 and a critical role in hyperactivated sperm motility and male fertility for PMCA4. J Biol Chem 279(32):33742-50PubMed: 15178683 MGI: J:91844

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Genetics

Atp2b4^tm1Ges

Allele Symbol: Atp2b4^tm1Ges

Allele Name	targeted mutation 1, Gary E Shull
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Pmca4^-
Gene Symbol and Name	Atp2b4, ATPase, Ca++ transporting, plasma membrane 4
Gene Synonym(s)
Strain of Origin	129X1/SvJ
Chromosome	1
Molecular Note	A region of exon 11 encoding amino acids 448-474, including the catalytic phosphorylation site (aspartic acid 465), was replaced with a neomycin resistance gene. Northern blot showed no reduction in mRNA levels in mutant mice. Exon-11-deficient mice express a mutant PMCA4 mRNA as a consequence of exon-10 splicing to exon-12, which preserves the reading frame and enables these mice to produce functionless mutant PMCA4a and PMCA4b proteins (devoid of a catalytic site).

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Cardiovascular Research
- Heart Abnormalities
  - cardiomyopathy
Cell Biology Research
- Channel and Transporter Defects
  - calcium
Immunology, Inflammation and Autoimmunity Research
- Immunodeficiency
  - B cell defects
Reproductive Biology Research
- Fertility Defects
  - males only
Internal/Organ Research
- Skeleton
  - Bone

Mammalian Phenotype Terms by Genotype

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

Genotype: Atp2b4^tm1Ges/Atp2b4^tm1Ges
involves: 129X1/SvJ * Black Swiss

behavior/neurological phenotype

excessive scratching
- excessive scratching is seen around the jaw and is correlated with an enlarged submandibular gland
- this phenotype is not seen on an inbred Black Swiss background

cardiovascular system phenotype

decreased vasoconstriction
- portal vein contractility is reduced and increased apoptosis is seen smooth muscle cells surrounding the portal vein after 4 hours in culture compared to wild-type mice

immune system phenotype

enlarged submandibular lymph nodes
- this phenotype is not seen on an inbred Black Swiss background
- the submandibular gland is enlarged

muscle phenotype

decreased vasoconstriction
- portal vein contractility is reduced and increased apoptosis is seen smooth muscle cells surrounding the portal vein after 4 hours in culture compared to wild-type mice

reproductive system phenotype

male infertility
- males but not females are infertile

Genotype: Atp2b4^tm1Ges/Atp2b4^tm1Ges
BKSW.129X1-Atp2b4

cellular phenotype

asthenozoospermia
- in hyperactivating conditions mutant sperm have significantly more condensed mitochondria compared to wild-type sperm
- hyperactivated sperm motility is severely impaired with most mutant sperm non-motile after 90 min in conditions that should result in hyperactivation
- mutant sperm have normal motility in the epididymis

reproductive system phenotype

male infertility
- males but not females are infertile

asthenozoospermia
- hyperactivated sperm motility is severely impaired with most mutant sperm non-motile after 90 min in conditions that should result in hyperactivation
- in hyperactivating conditions mutant sperm have significantly more condensed mitochondria compared to wild-type sperm
- mutant sperm have normal motility in the epididymis

References

Okunade GW; Miller ML; Pyne GJ; Sutliff RL; O'Connor KT; Neumann JC; Andringa A; Miller DA; Prasad V; Doetschman T; Paul RJ; Shull GE. 2004. Targeted ablation of plasma membrane Ca2+-ATPase (PMCA) 1 and 4 indicates a major housekeeping function for PMCA1 and a critical role in hyperactivated sperm motility and male fertility for PMCA4. J Biol Chem 279(32):33742-50PubMed: 15178683 MGI: J:91844

Additional - Atp2b4^tm1Ges related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Atp2b4
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice are bred as heterozygotes or homozygous female x heterozygous male. Male mice homozygous for the mutation are infertile.
- Additional Breeding and Husbandry Support
Citation
When using the FVB.129(Cg)-Atp2b4^tm1Ges/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #36807 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

Also Known As:FVB.Cg-Atp2b4tm1Ges/Mmjax

Donating Investigator

Genetic overview

Research Applications

Development

Control Suggestions

Additional Information

Selected References

Atp2b4tm1Ges

Allele Symbol: Atp2b4tm1Ges

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Atp2b4tm1Ges/Atp2b4tm1Gesinvolves: 129X1/SvJ * Black Swiss

behavior/neurological phenotype

cardiovascular system phenotype

immune system phenotype

muscle phenotype

reproductive system phenotype

Genotype: Atp2b4tm1Ges/Atp2b4tm1GesBKSW.129X1-Atp2b4

cellular phenotype

reproductive system phenotype

References

Additional - Atp2b4tm1Ges 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

Also Known As:FVB.Cg-Atp2b4^tm1Ges/Mmjax

Atp2b4^tm1Ges

Allele Symbol: Atp2b4^tm1Ges

Genotype: Atp2b4^tm1Ges/Atp2b4^tm1Ges
involves: 129X1/SvJ * Black Swiss

Genotype: Atp2b4^tm1Ges/Atp2b4^tm1Ges
BKSW.129X1-Atp2b4

Additional - Atp2b4^tm1Ges related