Strain Name:
C.Cg-Tg(SV40-HA*)HA28Ajca/Mmjax
Stock Number:
043825-JAX
Citation ID:
RRID:MMRRC_043825-JAX
Other Names:
HA28

Strain Information

SV40
Name: simian virus 40 early region promoter/enhancer
Type: DNA Segment
Species: Simian virus 40 (SV40)
Chromosome:
HA
Name: haemagglutinin, Influenza A virus (A/Puerto Rico/8/1934(H1N1))
Type: Gene
Species: Influenza virus
Chromosome:
Tg(SV40-HA*)HA28Ajca
Name: transgene insertion HA28, Andrew J Caton
Synonyms: HA28
Type: Transgene
Species: Influenza virus
Chromosome: random insertion
Alteration at locus: Transgenic
Genetic Alterations
The strain contains a transgene encoding the first 237 amino acids of the influenza virus A/PR/8/34 hemagglutinin (PR8 HA) under the control of the SV40 early region promoter/enhancer. More specifically, the construct used to generate the mice contains a nucleotide deletion which causes a frameshift followed by a stop codon, leading to expression of a truncated HA polypeptide containing the N-terminal signal sequence plus amino acids 1–237 of the mature PR8 HA (NP_040980.1).
Genotype Determination
ES Cell Line
Not specified
Phenotype

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.

MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Antibody-Producing Cells/immunology
  • Antigens, Viral/immunology
  • Autoantigens/biosynthesis
  • Autoantigens/genetics
  • Autoantigens/immunology
  • B-Lymphocyte Subsets/immunology
  • Base Sequence
  • Clone Cells
  • Enzyme-Linked Immunosorbent Assay
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Hemagglutinins, Viral/biosynthesis
  • Hemagglutinins, Viral/genetics
  • Hemagglutinins, Viral/immunology
  • Hybridomas
  • Immunoglobulin G/genetics
  • Immunoglobulin G/metabolism
  • Immunoglobulin Heavy Chains/genetics
  • Immunoglobulin Light Chains/genetics
  • Immunoglobulin Variable Region/genetics
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Molecular Sequence Data
  • Sequence Analysis, DNA
  • Antibody Specificity
  • Autoantibodies/genetics
  • Autoantibodies/immunology
  • Autoimmunity/immunology
  • B-Lymphocytes/cytology
  • B-Lymphocytes/immunology
  • B-Lymphocytes/metabolism
  • B-Lymphocytes/virology
  • CD4-Positive T-Lymphocytes/immunology
  • Cell Differentiation
  • Clone Cells/cytology
  • Clone Cells/immunology
  • Clone Cells/metabolism
  • Clone Cells/virology
  • Hemagglutinin Glycoproteins, Influenza Virus/genetics
  • Hemagglutinin Glycoproteins, Influenza Virus/immunology
  • Hybridomas/immunology
  • Immunization, Secondary
  • Immunoglobulin Variable Region/chemistry
  • Immunoglobulin Variable Region/immunology
  • Immunohistochemistry
  • Immunologic Memory/immunology
  • Influenza A virus/genetics
  • Influenza A virus/immunology
  • Lymph Nodes/cytology
  • Lymph Nodes/immunology
  • Mutation/genetics
  • Sequence Analysis
  • CD4-Positive T-Lymphocytes/cytology
  • CD4-Positive T-Lymphocytes/metabolism
  • Cells, Cultured
  • Clonal Deletion/immunology
  • Flow Cytometry
  • Forkhead Transcription Factors/immunology
  • Forkhead Transcription Factors/metabolism
  • Hemagglutinin Glycoproteins, Influenza Virus/metabolism
  • Interleukin-2 Receptor alpha Subunit/immunology
  • Interleukin-2 Receptor alpha Subunit/metabolism
  • Lymphocyte Activation/immunology
  • Peptides/immunology
  • Peptides/metabolism
  • Receptors, Antigen, T-Cell/genetics
  • Receptors, Antigen, T-Cell/immunology
  • Receptors, Antigen, T-Cell/metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Regulatory/cytology
  • T-Lymphocytes, Regulatory/immunology
  • T-Lymphocytes, Regulatory/metabolism
  • Thymus Gland/cytology
  • Thymus Gland/immunology
  • CD40 Antigens/physiology
  • CD40 Ligand/physiology
  • Forkhead Transcription Factors/genetics
  • Interleukin-2/pharmacology
  • Isoantigens/immunology
  • Mice, Inbred C57BL
  • Sirolimus/pharmacology
  • T-Lymphocytes, Regulatory/physiology
  • Transforming Growth Factor beta/pharmacology
  • Transplantation Tolerance
  • Transplantation, Homologous
  • DNA-Binding Proteins/genetics
  • Disease Models, Animal
  • Graft vs Host Disease/immunology
  • Phenotype
  • Stem Cell Transplantation/adverse effects
  • T-Lymphocytes/immunology
Strain Development
Backcrossed 13 generations with BALB/cAnNCrl (Charles River Strain Code 028), then intermated to homozygosity. Maintained as homozygotes. Upon arrival at the MMRRC: backcrossing to BALB/cByJ (Jackson Strain #001026).
Suggested Control Mice
Wild-type littermates
MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact csmmrrc@jax.org. Older strains may not have this information.
  • Cancer
  • Diabetes
  • Immunology and Inflammation
  • Research Tools
Donor
Andrew J. Caton, Ph.D., The Wistar Institute.
Primary Reference

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)

Colony and Husbandry Information

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...."

This led to a lot of confusion over the years, suggesting errors in the PR8 HA sequence when other investigators worked with the donor's virus or transgenic mice. Likely, no database lists the PR8 (Mount Sinai) sequence, because it was never published as a de novo sequence. It was inferred from the analysis of a number of mutant viruses in the donor's publication, but this was based on an analysis of only about half of the HA sequence and never the complete gene. Later, Scott Hensley sequenced the substrain of the PR8 HA used to make the mice; the information can be found here: https://www.ncbi.nlm.nih.gov/nuccore/CY084006.1

It should be noted that this PR8 (Mount Sinai) strain was also used to generate the HA104 (MMRRC:43831) and HACII mice (MMRRC:43832) deposited by the same donor: their HA transgenes will have the nucleotide substitutions relative to the published reference PR8 HA sequence. However, the HA transgenes in HA104 and HACII mice do not have the nucleotide deletion that is in the HA28 transgene; a fortuitous error that occurred during the cloning process for the HA28 mice.

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.

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email csmmrrc@jax.org.
Coat Color
Albino
MMRRC Breeding System
Backcross then sib-mating
Generation
N13 (BALB/cAnNCrl, Charles River Strain Code 028), F12-15
Overall Breeding Performance
Good
NOTE: "Hemizygote" as used here refers to males carrying a mutation on the X Chromosome or mice of either sex carrying an inserted transgene with no homologous allele on the other chromosome.
Viability and Fertility: Female Male Comments
Homozygotes are viable: Yes Yes
Homozygotes are fertile: Yes Yes
Hetero/Hemizygotes are fertile: Yes Yes
Age Reproductive Decline: 8 to 12 months 8 to 12 months
Bred to Homozygosity
No
Average litter size
4-6
Recommended wean age
3-4 weeks
Average Pups Weaned
4-6

Order Request Information

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.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*
Units Notes
043825-JAX-SPERM Cryo-preserved spermatozoa $437.00 / Non-Profit Aliquot Approximate quantity3
043825-JAX-RESUS Litter recovered from cryo-archive $2,022.00 / Non-Profit Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to csmmrrc@jax.org for more information.

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.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.