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The VIVIT peptide (MAGPHPVIVITGPHEE) is a cell-permeable peptide inhibitor of NFATC1-4 (nuclear factor of activated T cells, cytoplasmic, calcineurin dependent) that selectively inhibits calcineurin-mediated dephosphorylation of NFATC but does not compromise calcineurin phosphatase activity and non-NFAT-mediated signaling. Nfatc functions as an immune regulatory transcription factor. iNFATuation knock-in mice were created using the FLEx methodology (GENOway), which uses two different lox sites (loxP and lox2272) that can only recombine with sites of the same type. loxP and lox2272 are set in opposing orientations such that Cre recombinase inverts the CAG promoter between the sites allowing tissue specific expression of the VIVIT peptide and the tdTomato reporter. The targeting construct was inserted in the Gt(ROSA)26Sor locus. Mice homozygous for the mutation are viable and fertile. When bred to mice with cre expression in Platelets (Tg(Pf4-icre)Q3RskJ, Stock No. 008538), platelets isolated from double mutant progeny and activated in vitro exhibit reduced NFATC1 dephosphorylation, and an increase in the aggregation and P-selectin expression of activated, but not resting cells.
Poli V, Di Gioia M, Sola-Visner M, Granucci F, Frelinger AL 3rd, Michelson AD, Zanoni I. Inhibition of transcription factor NFAT activity in activated platelets enhances their aggregation and exacerbates gram-negative bacterial septicemia. Immunity. 2022 Feb 8;55(2):224-236.e5. doi: 10.1016/j.immuni.2021.12.002. Epub 2022 Jan 6. (Medline PMID: 34995475)
Limited quantities of breeder mice (up to 2 males and 2 females or 4 mice) per investigator per month are available from a live colony, usually available to ship in under 12 weeks. Larger quantities may be available, please contact the distributing center directly at csmmrrc@jax.org for more details.
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.