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Atp2b4 or PMCA4 (Ca++ transporting ATPase, plasma membrane 4) encodes a P-type primary ion transport ATPase. This ATPase is involved in intracellular calcium homeostasis and is expressed in aorta, portal vein, bladder, diaphragm, seminal vesicles, and testis.Mice homozygous for this null allele are viable, however, male mice are infertile. Male infertility is due to loss of the the major plasma membrane Ca-ATPase (PMCA) of the sperm tail, resulting in the inability of sperm to achieve the hyperactivated motility needed for fertilization.On a mixed 129 and Black Swiss background, portal vein smooth muscle cells from homozygous mice exhibit increased apoptosis and reduced phasic contractions. Mice on the mixed background develop enlarged submandibular glands, skin irritation, accelerated osteoclastogenesis, osteopenia with an increase in osteoclasts on bone surface, and attenuated Ca signaling in B lymphocytes. On a congenic FVB background, homozygotes exhibit 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.
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. 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. 2004 Aug 6;279(32):33742-50. (Medline PMID: 15178683)
Wu X, Chang B, Blair NS, Sargent M, York AJ, Robbins J, Shull GE, Molkentin JD. Plasma membrane Ca2+-ATPase isoform 4 antagonizes cardiac hypertrophy in association with calcineurin inhibition in rodents. J Clin Invest. 2009 Apr;119(4):976-85. (Medline PMID: 19287093)
Chen J, McLean PA, Neel BG, Okunade G, Shull GE, Wortis HH. CD22 attenuates calcium signaling by potentiating plasma membrane calcium-ATPase activity. Nat Immunol. 2004 Jun;5(6):651-7. (Medline PMID: 15133509)
Liu L, Ishida Y, Okunade G, Pyne-Geithman GJ, Shull GE, Paul RJ. Distinct roles of PMCA isoforms in Ca2+ homeostasis of bladder smooth muscle: evidence from PMCA gene-ablated mice. Am J Physiol Cell Physiol. 2007 Jan;292(1):C423-31. (Medline PMID: 16956963)
Kim HJ, Prasad V, Hyung SW, Lee ZH, Lee SW, Bhargava A, Pearce D, Lee Y, Kim HH. Plasma membrane calcium ATPase regulates bone mass by fine-tuning osteoclast differentiation and survival. J Cell Biol. 2012 Dec 24;199(7):1145-58. (Medline PMID: 23266958)
Cryo-recovered strains distributed by the MMRRC at JAX are shipped to the customer from the Pathogen & Opportunistic-Free Animal Room G200 - see https://www.jax.org/jax-mice-and-services/customer-support/customer-service/animal-health/health-status-reports.
Wild-type (FVB/N) female x Heterozygous male or reciprocal mating.
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.
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.