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Strain Name:
B6J.Cg-Ptprctm1Holm Tg(ITGAL-Ptprca)HRasch/Mmucd
Stock Number:
046256-UCD
Citation ID:
RRID:MMRRC_046256-UCD
Other Names:
CD45 minigene strain H

Strain Information

Ptprctm1Holm
Name: protein tyrosine phosphatase receptor type C; targeted mutation 1, Nick Holmes
Synonyms: CD45-, Ptprctm1, CD45-exon9
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 1
Alteration at locus: Knockout
Ptprc
Name: protein tyrosine phosphatase receptor type C
Synonyms: T200, B220, CD45, Lyt-4, Ly-5
Type: Gene
Species: Mouse
Chromosome: 1
Alteration at locus: Transgenic (random, gene disruption)
NCBI: 19264
HGNC: HGNC:9666
Homologene: 2126
Ptprca
Name: protein tyrosine phosphatase receptor type C; a variant
Synonyms: CD45.1, Ly5a, PtprcSJL
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 1
Alteration at locus: Transgenic (random, gene disruption)
Tg(ITGAL-Ptprca)HRasch
Name: transgene insertion H, William C Raschke
Type: Allele
Species: Multi-species
Chromosome: unknown
Alteration at locus: Transgenic (random, gene disruption)
ITGAL
Name: integrin subunit alpha L
Type: Regulatory Region
Species: Homo sapiens (human)
Chromosome: 16
Alteration at locus: Transgenic (random, gene disruption)
Genetic Alterations
These animals carry a knockout of the Ptprc gene (synonym: CD45, Ptprctm1Holm - MGI:1857277). The same gene was re-introduced as a CD45 mini/transgene in unknown chromosome location. The minigene is composed of 33 exons (1b through 33) and the sequence is genomic between exons 3 and 9. The inclusion of the introns is critical for the high-level expression from the transgene and for the cell-type specific, regulated expression of the CD45 isoforms. The design of the minigene VGI-0020 (also published as "pLFAiT200") is described in PMID:11389149.

The MMRRC holds three sibling strains B (MMRRC:44051), F (MMRRC:46054), and H (MMRRC:46256), which differ in the transgene copy number (integrated as concatemers into the genome) and therefore express different levels of CD45 protein (where H > F > B). The number of transgene copies in each concatemer was random and a result of the process of transgene incorporation into the zygote.
Genotype Determination
ES Cell Line
R1 derived from (129X1/SvJ x 129S1/Sv)F1-Kitl+ (for the development of the Ptprctm1Holm allele)
Phenotype
Strain H is one of three transgenic strains prepared with the CD45/Ptprc minigene; it expresses the highest amounts of CD45 at 125% of the wild-type level. When the two H transgene loci are present in C57BL/6 mice with two functional endogenous CD45 genes, termed "HE" mice, the expression level is 180% of the wild-type level. The transgene encodes the CD45.1 allelic sequence (LY5a, Ptprca - MGI:4819849), which is detected by anti-CD45.1 antibodies. The strain has no breeding, lifespan, or general health deficiencies. Normal hematopoietic lineage and maturation-specific isoform regulation of the transgene product is maintained due to the inclusion of the natural introns between exons 3 and 9 in the transgene DNA sequence.

Note: The transgene encodes the CD45.1 (LY5a, Ptprca) sequence, whereas the remaining background of the CD45 knockout strain, onto which the transgene was backcrossed, is C57BL/6 (JAX Strain #002725). In fact, the non-functional, endogenous gene in the knockout strain (JAX Strain #002527) is CD45.2 (Ly5b, Ptprcb - MGI:4819850), but no CD45.2 protein is expressed. Thus, in transgenic strains B (MMRRC:44051), F (MMRRC:46054), and H (MMRRC:46256), only the CD45 protein from the transgene is expressed and has the CD45.1 sequence and anti-CD45.1 antibody reactivity.
Mammalian Phenotype Terms
Allelic Composition: (Genetic Background: )

MeSH Terms
  • ADP-ribosyl Cyclase
  • ADP-ribosyl Cyclase 1
  • Animals
  • Antigens, CD
  • Antigens, Differentiation/metabolism
  • B-Lymphocytes/immunology
  • CD40 Antigens/metabolism
  • Hematopoietic Stem Cells/immunology
  • Immunoglobulin D/biosynthesis
  • Immunoglobulin M/biosynthesis
  • Leukocyte Common Antigens/genetics
  • Leukocyte Common Antigens/metabolism
  • Lymphocyte Activation
  • Lymphocytes/immunology
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • N-Glycosyl Hydrolases/metabolism
  • Organ Culture Techniques
  • Receptors, Antigen/metabolism
  • Selection, Genetic
  • Signal Transduction
  • Spleen/cytology
  • Spleen/immunology
  • T-Lymphocyte Subsets/immunology
  • Thymus Gland/cytology
  • Thymus Gland/growth & development
  • Anthrax/enzymology
  • Anthrax/prevention & control
  • Antigens, Bacterial/metabolism
  • Antigens, Bacterial/toxicity
  • Apoptosis
  • Bacillus anthracis/pathogenicity
  • Bacillus anthracis/physiology
  • Bacterial Toxins/antagonists & inhibitors
  • Bacterial Toxins/metabolism
  • Bacterial Toxins/toxicity
  • Cell Survival
  • Female
  • Flow Cytometry
  • Gene Knockdown Techniques
  • Genetic Testing
  • Immunoblotting
  • Immunoenzyme Techniques
  • Leukocyte Common Antigens/antagonists & inhibitors
  • Macrophages/microbiology
  • Male
  • Mice, Inbred BALB C
  • Morpholines/pharmacology
  • Morpholinos
  • Phagocytosis
  • Phosphoric Monoester Hydrolases/metabolism
  • Spores, Bacterial/growth & development
  • Spores, Bacterial/pathogenicity
  • CD8-Positive T-Lymphocytes/immunology
  • Disease Susceptibility
  • Ebolavirus/immunology
  • Ebolavirus/pathogenicity
  • Gene Expression Profiling
  • Host-Pathogen Interactions
  • Humans
  • Interferon-gamma/immunology
  • Leukocyte Common Antigens/immunology
  • Lymph Nodes/virology
  • Macrophages, Peritoneal/virology
  • Models, Biological
  • Spleen/virology
  • Survival Analysis
  • 3' Untranslated Regions
  • DNA, Complementary
  • Introns
  • Jurkat Cells
  • Lymphocyte Function-Associated Antigen-1/genetics
  • Promoter Regions, Genetic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Antibody Formation
  • B-Lymphocytes/cytology
  • Gene Expression Regulation/genetics
  • Immunity/genetics
  • Leukocyte Common Antigens/biosynthesis
  • Protein Isoforms/biosynthesis
  • Protein Isoforms/genetics
  • Severe Combined Immunodeficiency/therapy
  • T-Lymphocytes/cytology
  • T-Lymphocytes/immunology
  • Thyroid Gland/cytology
  • Transcription, Genetic
  • Transgenes/genetics
Strain Development

The CD45-minigene transgenic construct 'VGI-0020' (also shown as LFAiT200 in reference PMID:12393487) was injected into (BALB/c x C57BL/6)F2 oocytes. This line is "Strain B", which was 1 of 3 founders. The Strain H founder was mated to C57BL/6J mice (JAX Strain #002725) and progeny were screened for the presence of the transgene. The colony was then backcrossed to C57BL/6J mice for 10 generations. The colony was crossed with the CD45 knockout strain on the C57BL/6 background until the transgene locus was homozygous on the CD45 knockout background. Mice homozygous for the Strain B transgene locus on the CD45 knockout background were then sib-mated after the backcrossing was complete, for at least 25 generations to date.

Suggested Control Mice
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 mmrrc@ucdavis.edu. Older strains may not have this information.
  • Developmental Biology
  • Hematology
  • Immunology and Inflammation
  • Models for Human Disease
Donor
William Raschke, Ph.D Virogenics
Primary Reference

Byth KF, Conroy LA, Howlett S, Smith AJ, May J, Alexander DR, Holmes N.CD45-null transgenic mice reveal a positive regulatory role for CD45 in earlythymocyte development, in the selection of CD4+CD8+ thymocytes, and B cellmaturation. J Exp Med. 1996 Apr 1;183(4):1707-18. (Medline PMID: 8666928)

Panchal RG, Ulrich RL, Bradfute SB, Lane D, Ruthel G, Kenny TA, Iversen PL,Anderson AO, Gussio R, Raschke WC, Bavari S. Reduced expression of CD45protein-tyrosine phosphatase provides protection against anthrax pathogenesis. J Biol Chem. 2009 May 8;284(19):12874-85. doi: 10.1074/jbc.M809633200. Epub 2009Mar 6. (Medline PMID: 19269962)

Panchal RG, Bradfute SB, Peyser BD, Warfield KL, Ruthel G, Lane D, Kenny TA,Anderson AO, Raschke WC, Bavari S. Reduced levels of protein tyrosine phosphataseCD45 protect mice from the lethal effects of Ebola virus infection. Cell HostMicrobe. 2009 Aug 20;6(2):162-73. doi: 10.1016/j.chom.2009.07.003. (Medline PMID: 19683682)

Virts EL, Raschke WC. The role of intron sequences in high level expressionfrom CD45 cDNA constructs. J Biol Chem. 2001 Jun 8;276(23):19913-20. Epub 2001Mar 16. (Medline PMID: 11389149)

Virts EL, Diago O, Raschke WC. A CD45 minigene restores regulated isoformexpression and immune function in CD45-deficient mice: therapeutic implicationsfor human CD45-null severe combined immunodeficiency. Blood. 2003 Feb1;101(3):849-55. Epub 2002 Sep 19. (Medline PMID: 12393487)

Colony and Husbandry Information

Colony Surveillance Program and Current Health 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 mmrrc@ucdavis.edu.
Coat Color
Black
Eye
Black
Other
CD45-minigene transgenic strain H on the CD45 knockout C57BL/6 background expresses 125% of the wild-type level of CD45. The transgene encodes the CD45.1 allelic sequence which is detected by anti-CD45.1 antibodies. The strain has no breeding, lifespan or general health deficiencies.
MMRRC Breeding System
Sib-mating
Generation
N10F25+
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
Average litter size
7-9
Recommended wean age
4 weeks
Average Pups Weaned
5-9

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 mmrrc@ucdavis.edu 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.

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
046256-UCD-EMBRYO Cryo-preserved embryos $1,038.00 / $1,568.61
Non-Profit / For-Profit
Aliquot Approximate quantity2 : 20-40 embryos / aliquot
046256-UCD-SPERM Cryo-preserved spermatozoa $546.25 / $882.81
Non-Profit / For-Profit
Aliquot Approximate quantity3
046256-UCD-RESUS Litter recovered from cryo-archive $4,044.00 / $7,650.23
Non-Profit / For-Profit
Litter Recovered litter4; additional fees for any special requests.

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.