The catalytic domain is disrupted in this Ppp3ca (protein phosphatase 3, catalytic subunit, alpha isoform) knockout allele. Animals generate defective antigen-specific T cell responses in vivo, hyperphosphorylated tau accumulates in the mossy fibers of the hippocampus, and their kidneys fail to develop. Most homozygotes die between 2 and 4 weeks of age due to a salivary gland/early digestion defect.
Jennifer Gooch, Emory University
Genetic Background | Generation |
---|---|
|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Null/Knockout) | Ppp3ca | protein phosphatase 3, catalytic subunit, alpha isoform |
Ppp3ca (protein phosphatase 3, catalytic subunit, alpha isoform) is a calcium- and calmodulin-dependent serine/threonine protein phosphatase. It is an important signaling molecule in T cells, neurons, the heart, and kidneys.
The catalytic domain of Ppp3ca has been disrupted in this knockout allele. Although the composition and distribution of T cell subsets is normal in homozygous knockout mice, and in vitro responses to mitogenic stimulation are similar to those of wildtype, the animals generate defective antigen-specific T cell responses in vivo.
Hyperphosphorylated tau, the major component of the helical filaments of Alzheimer's disease, accumulates in the brains of homozygous animals. This accumulation occurs particularly in the mossy fibers of the hippocampus, which contain the highest level of calcineurin in the brains of wildtype mice. The mossy fibers exhibit abnormalities in their cytoskeleton and a lower neurofilament/microtubule ratio than those of wildtype animals. Other Ppp3ca-deficient strains have been shown to have deficits in learning and memory that may result in part from these changes.
The kidneys of homozygotes fail to develop. Postnatal maturation of the nephrogenic zone is defective. Glomeruli also fail to mature in the nephrogenic zone and lack mesangial cells. Cells fail to proliferate and show an increase in cell death in the nephrogenic zone. There is an increase in collagen deposition and serum creatinine levels are increased. Water channel AQP2 (aquaporin 2) is mislocalized in the kidney collecting duct.
Homozygous mice fail to thrive and most die between 2 and 4 weeks of age due to a salivary gland/early digestion defect. Powdered rodent chow suspended in 1.5% gelatin or PancreVed digestive enzymes (VEDCO, NDC: 50989-771-25) in peanut oil added to moistened chow pellets rescues knockout animals and enables them to survive to adulthood. Loss of protein results in impaired salivary gland vesicular protein trafficking downstream of the inositol triphosphate receptor.
A neomycin cassette was inserted into the exon encoding part of the catalytic domain of the protein (bp 572 - 717 of the mRNA) via homologous recombination in 129S4/SvJae-derived J1 embryonic stem (ES) cells. Resultant chimeric mice were crossed with Black Swiss and C57BL/6 animals. This strain was maintained on a mixed genetic background by the donating laboratory.
Allele Name | targeted mutation 1, Jonathan G Seidman |
---|---|
Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | Aalpha-; CnA alpha (_); CNAa-; CnA-alpha- |
Gene Symbol and Name | Ppp3ca, protein phosphatase 3, catalytic subunit, alpha isoform |
Gene Synonym(s) | |
Strain of Origin | 129S4/SvJae |
Chromosome | 3 |
Molecular Note | A neomycin cassette was inserted into the exon encoding nucleotides 572 - 717 of the mRNA sequence of the gene. This exon encodes part of the catalytic domain of the protein. Western blots of T cell extracts from homozygous mutant mice showed no detectable peptide. |
Heterozygotes are viable and fertile. Homozygous mice fail to thrive and most die between 2 and 4 weeks of age due to a salivary gland/early digestion defect. Powdered rodent chow suspended in 1.5% gelatin or PancreVed digestive enzymes in peanut oil (0.16 g powder in 30 ml oil) added to moistened chow pellets rescues knockout animals and enables them to survive to adulthood. Homozygotes that survive to maturity are fertile.
When using the STOCK Ppp3catm1Jse/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #024064 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Ppp3ca<tm1Jse> |
Frozen Mouse Embryo | STOCK Ppp3ca<tm1Jse>/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | STOCK Ppp3ca<tm1Jse>/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | STOCK Ppp3ca<tm1Jse>/J Frozen Embryos | $3373.50 |
Frozen Mouse Embryo | STOCK Ppp3ca<tm1Jse>/J Frozen Embryos | $3373.50 |
Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.
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.
What information were you hoping to find through your search?
How easy was it to find what you were looking for?
We may wish to follow up with you. Enter your email if you are happy for us to connect and reachout to you with more questions.
Please Enter a Valid Email Address
Thank you for sharing your feedback! We are working on improving the JAX Mice search. Come back soon for exciting changes.