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Homozygous: Non-lethal. No abnormal physiology detected.
Hetero/Hemizygous: No abnormal physiology detected. Induces CD4+ T cell tolerance to encoded epitopes from HA. When mated with Tg(Tcra/Tcrb)1Vbo mice induces abundant formation of HA-specific CD4+Foxp3+ regulatory T cells.
Caton AJ, Swartzentruber JR, Kuhl AL, Carding SR, Stark SE. Activation andnegative selection of functionally distinct subsets of antibody-secreting cellsby influenza hemagglutinin as a viral and a neo-self antigen. J Exp Med. 1996 Jan1;183(1):13-26. (Medline PMID: 8551216)
Reed AJ, Riley MP, Caton AJ. Virus-induced maturation and activation of autoreactive memory B cells. J Exp Med. 2000 Dec 18;192(12):1763-74. (Medline PMID: 11120773)
Picca CC, Oh S, Panarey L, Aitken M, Basehoar A, Caton AJ. Thymocyte deletion can bias Treg formation toward low-abundance self-peptide. Eur J Immunol. 2009 Dec;39(12):3301-6. doi: 10.1002/eji.200939709. (Medline PMID: 19768697)
Kim JI, O'connor MR, Duff PE, Zhao G, Lee KM, Eliades P, Deng S, Yeh H, Caton AJ, Markmann JF. Generation of adaptive regulatory T cells by alloantigen is required for some but not all transplant tolerance protocols. Transplantation. 2011 Apr 15;91(7):707-13. doi: 10.1097/TP.0b013e31820e50b3. (Medline PMID: 21386770)
Juchem KW, Anderson BE, Zhang C, McNiff JM, Demetris AJ, Farber DL, Caton AJ, Shlomchik WD, Shlomchik MJ. A repertoire-independent and cell-intrinsic defect inmurine GVHD induction by effector memory T cells. Blood. 2011 Dec1;118(23):6209-19. doi: 10.1182/blood-2011-01-330035. Epub 2011 Jul 18. (Medline PMID: 21768295)
The nucleotide and amino acid sequences are of the “reference” sequences of the HA gene for the PR8 strain of influenza virus. This sequence was determined by Winter et al. (PMID:7278968) based on an analysis of PR8 virus that had been grown out of freezers in the University of Cambridge in the UK. The version of PR8 virus that the donor (A. Caton) worked with to generate the mice archived at the MMRRC had been obtained from Mount Sinai Medical School in New York. During sequence studies on the HA gene of this virus, A. Caton discovered that the “version” of PR8 used had a number of nucleotide and amino acid substitutions relative to the “reference” sequence of PR8 that had previously been published. It was deduced that there were different substrains of PR8 virus that had drifted from each other during several decades of passage at the different laboratories (note that the original PR8 strain had been isolated in Puerto Rico in 1934) The donor called the substrain used “PR8 (Mount Sinai)”, and called the previously described reference substrain “PR8 (Cambridge)”. The differences are reported in Caton et al., Cell vol 31 417 1982 (PMID:6186384):
"...These primers allowed the determination of the nucleotide sequence of the region of the genome encoding the mature (without signal peptide) HA1 polypeptide of influenza virus A/PR/8/34 (Mount Sinai), from which the various mutants were derived (Figure 1). This nucleotide sequence shows 12 differences, including a three-base deletion, when compared with that of PR8 (Cambridge) (Winter et al., 1981), which code for seven different amino acid residues and one amino acid deletion. The deletion of an A3 triplet-nucleotides 471-473 in PR8 (Cambridge)-results in the absence from PR8 (Mount Sinai) of the lysine residue 130 residues from the amino terminus of the mature HA1 of PR8 (Cambridge). The C to A difference at position 469 means that the potential carbohydrate attachment sequence (Asn-X-Ser or Asn-X-Thr; published in [Carbohydrate-peptide linkages in glycoproteins and methods for their elucidation, A. Gottschalk (Ed.), Glycoproteins; Their Composition, Structure and Function, Elsevier, Amsterdam (1972), pp. 450-490]) at amino acid residues 127-129 of PR8 (Cambridge) is absent from PR8 (Mount Sinai). The differences in sequence presumably represent the variation that has occurred during the independent laboratory passage of virus which was originally isolated from the same source. It is clear from this that the description of a prototype sequence as the definitive sequence for any virus subtype, or particularly for any virus strain, must be viewed with caution...."
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.
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.