Overview

Also Known As:B6.Cg-Atp2c1^tm1Ges/Mmjax

Aging mice heterozygous for a null Atp2c1 or SPCA1 (Ca++ sequestering ATPase) allele develop an increased incidence (25%) of squamous cell tumors of keratinized epithelial cells of the skin and esophagus. Homozygous embryos do not survive beyond E10.5 as a result of Golgi stress. This strain may be useful for studying Golgi stress and its role in cancer.

Donating Investigator

Gary E Shull, University of Cincinnati

Genetic overview

Genetic Background	Generation

Atp2c1^tm1Ges

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Atp2c1	ATPase, Ca++-sequestering

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Research Applications

Developmental Biology Research
Cancer Research
Cell Biology Research

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Details

Detailed Description

Atp2c1 or SPCA1 (Ca++ sequestering ATPase) encodes a secretory pathway Ca<2+>-ATPase located in the Golgi. This ATPase mediates Golgi uptake and regulation of cytosolic calcium and magnesium ions. Homozygous embryos do not survive beyond E10.5 as a result of Golgi stress. On a Black Swiss background, embryos exhibit incomplete neural tube closure, diminished Golgi lamellae, dilation of Golgi membranes, increased numbers of Golgi bodies, decreased numbers of ribosomes in the rough ER, increased apoptosis, and an increase in cytoplasmic lipids.
Mice heterozygous for this allele on a mixed 129 and Black Swiss background are viable and fertile, however aged (20+ months) mice have an increased incidence (25%) of squamous cell tumors of keratinized epithelial cells of the skin and esophagus.

This strain may be useful for studying Golgi stress and its role in cancer.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector containing the neomycin resistance gene was used to replace exons 10-13, representing a region which includes the catalytic phosphorylation site and transmembrane domains 3 and 4. 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 C57BL/6 for at least 6 generations. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Okunade GW; Miller ML; Azhar M; Andringa A; Sanford LP; Doetschman T; Prasad V; Shull GE. 2007. Loss of the Atp2c1 Secretory Pathway Ca2+-ATPase (SPCA1) in Mice Causes Golgi Stress, Apoptosis, and Midgestational Death in Homozygous Embryos and Squamous Cell Tumors in Adult Heterozygotes. J Biol Chem 282(36):26517-27PubMed: 17597066 MGI: J:124662

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Genetics

Atp2c1^tm1Ges

Allele Symbol: Atp2c1^tm1Ges

Allele Name	targeted mutation 1, Gary E Shull
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Spca1^-
Gene Symbol and Name	Atp2c1, ATPase, Ca++-sequestering
Gene Synonym(s)
Strain of Origin	129X1/SvJ
Chromosome	9
Molecular Note	A neomycin selection cassette replaced exons 10-13, which encode both the catalytic phosphorylation domain and transmembrane domains 3 and 4. RT-PCR and sequencing analysis revealed expression of a mutant mRNA in which exon 9 is spliced to exon 14. Western analysis revealed decreased protein expression in heterozygous mice

Disease/Phenotype

Disease Terms

No similarity to the expected human disease phenotype was found. One or more human genes are associated with this human disease. The mouse genotype may involve mutations to orthologs of one or more of these genes, but the phenotype did not resemble the disease.

Hailey-Hailey disease

Research Areas By Phenotype

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

Developmental Biology Research
- Neural Tube Defects
- Embryonic Lethality (Homozygous)
Cancer Research
- Increased Tumor Incidence
  - Skin Cancers
Cell Biology Research
- Channel and Transporter Defects
  - calcium

Mammalian Phenotype Terms by Genotype

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

Genotype: Atp2c1^tm1Ges/Atp2c1^tm1Ges
involves: 129X1/SvJ * Black Swiss

growth/size/body region phenotype

embryonic growth retardation
- growth restriction occurs between E8.5-E10.5 of development

increased head mesenchyme apoptosis
- increased apoptosis of cells within the head mesenchyme particularly in the area of the trigeminal neural crest at E8.5-E10.5

decreased embryo size
- prior to death at E10.5, embryos are smaller than wild-type controls

mortality/aging

embryonic lethality during organogenesis, complete penetrance
- embryos die between E10.5 and E11.5 due to widespread failure of cell viability

nervous system phenotype

exencephaly

open neural tube
- embryos exhibit a failure of neural tube closure from the hindbrain rostrally

abnormal embryonic neuroepithelium morphology
- at E10.5 ruffles are seen in the neuroectoderm of the neural tube of some embryos

increased neural tube apoptosis
- increased apoptosis in neural tube at E8.5-E10.5

cellular phenotype

abnormal Golgi apparatus morphology
- embryonic cells display a 4-fold increase in Golgi body number and the Golgi bodies have dilated membranes and an increase in smooth and dense vesicles

abnormal cell morphology
- a sharp increase is seen in the number of cells with 3 or more lipid droplets in the cytoplasm particularly in the mesenchyme and cardiovascular tissues at E8.5 - E10.5

increased head mesenchyme apoptosis
- increased apoptosis of cells within the head mesenchyme particularly in the area of the trigeminal neural crest at E8.5-E10.5

increased neural tube apoptosis
- increased apoptosis in neural tube at E8.5-E10.5

abnormal endoplasmic reticulum morphology
- the rough endoplasmic reticulum has fewer ribosomes compared to wild-type embryonic cells

embryo phenotype

decreased embryo size
- prior to death at E10.5, embryos are smaller than wild-type controls

open neural tube
- embryos exhibit a failure of neural tube closure from the hindbrain rostrally

abnormal embryonic neuroepithelium morphology
- at E10.5 ruffles are seen in the neuroectoderm of the neural tube of some embryos

increased head mesenchyme apoptosis
- increased apoptosis of cells within the head mesenchyme particularly in the area of the trigeminal neural crest at E8.5-E10.5

embryonic growth retardation
- growth restriction occurs between E8.5-E10.5 of development

Genotype: Atp2c1^tm1Ges/Atp2c1⁺
involves: 129X1/SvJ * Black Swiss

digestive/alimentary phenotype

increased esophageal papilloma incidence
- of the 6 mice with squamous cell carcinomas two had an esophageal papilloma at 22 months of age

integument phenotype

increased skin papilloma incidence
- of the 6 mice with squamous cell carcinomas one had a skin papilloma at 2 years of age

neoplasm

increased esophageal papilloma incidence
- of the 6 mice with squamous cell carcinomas two had an esophageal papilloma at 22 months of age

increased squamous cell carcinoma incidence
- 3 of the 6 mice with squamous cell carcinomas had carcinomas of the skin at 20 - 22 months of age
- 6 of 26 mice (over 20 months of age) displayed squamous cell tumors of keratinized epthelial cells compared to 0 wild-type mice at the same age

increased skin papilloma incidence
- of the 6 mice with squamous cell carcinomas one had a skin papilloma at 2 years of age

References

Okunade GW; Miller ML; Azhar M; Andringa A; Sanford LP; Doetschman T; Prasad V; Shull GE. 2007. Loss of the Atp2c1 Secretory Pathway Ca2+-ATPase (SPCA1) in Mice Causes Golgi Stress, Apoptosis, and Midgestational Death in Homozygous Embryos and Squamous Cell Tumors in Adult Heterozygotes. J Biol Chem 282(36):26517-27PubMed: 17597066 MGI: J:124662

Additional - Atp2c1^tm1Ges related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Atp2c1
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice are bred as heterozygotes. Mice homozygous for the mutation are not viable.
- Additional Breeding and Husbandry Support
Mating System
- Wild-type x Heterozygote
- Heterozygote x Wild-type
Citation
When using the B6.129X1(Cg)-Atp2c1^tm1Ges/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #36808 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:B6.Cg-Atp2c1tm1Ges/Mmjax

Donating Investigator

Genetic overview

Research Applications

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Atp2c1tm1Ges

Allele Symbol: Atp2c1tm1Ges

Disease Terms

No similarity to the expected human disease phenotype was found. One or more human genes are associated with this human disease. The mouse genotype may involve mutations to orthologs of one or more of these genes, but the phenotype did not resemble the disease.

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Atp2c1tm1Ges/Atp2c1tm1Gesinvolves: 129X1/SvJ * Black Swiss

growth/size/body region phenotype

mortality/aging

nervous system phenotype

cellular phenotype

embryo phenotype

Genotype: Atp2c1tm1Ges/Atp2c1+involves: 129X1/SvJ * Black Swiss

digestive/alimentary phenotype

integument phenotype

neoplasm

References

Additional - Atp2c1tm1Ges related

Genotyping Protocols

Breeding Considerations

Mating System

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:B6.Cg-Atp2c1^tm1Ges/Mmjax

Atp2c1^tm1Ges

Allele Symbol: Atp2c1^tm1Ges

Genotype: Atp2c1^tm1Ges/Atp2c1^tm1Ges
involves: 129X1/SvJ * Black Swiss

Genotype: Atp2c1^tm1Ges/Atp2c1⁺
involves: 129X1/SvJ * Black Swiss

Additional - Atp2c1^tm1Ges related