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Strain Name:

B6;129S2-Cd40lgtm1Imx/J

Stock Number:

002428

Availability:

Repository-Cryopreserved

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General Terms and Conditions

Former Name      B6;129S2-Tnfsf5tm1Imx/J    (Changed: 30-SEP-05 )
      Cd40l    (Changed: 15-DEC-04 )
Genes & Alleles   Cd40lg;   Cd40lgtm1Imx;

Product Information

Strain Details

Type JAX® GEMM® Strain - Mutant Stock
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Targeted Mutation
Specieslaboratory mouse
Donating Investigator Jacques Peschon,   Amgen Washington
GenerationF?+5pN1

Appearance
white bellied agouti
Related Genotype: Aw/?

black
Related Genotype: a/a

Strain Description
Mice homozygous for the targeted mutation are viable and fertile. Homozygous mutant mice show no overt phenotypic abnormalities. Percentages of B and T cell subpopulations is normal. Homozygotes do show selective deficiencies in humoral immunity (low basal serum isotype levels and undetectable IgE) as well as abnormal secondary antigen-specific responses to immunization with a thymus-dependent antigen. The phenotype of the mice resembles human X-linked hyper IgM syndrome.

Strain Development
This targeted mutation was created by replacing exons 3 and 4 with a PGKneo cassette using gene targeting by homologous recombination in 129S2/SvPas-derived D3 embryonic stem (ES) cells.

Related Disease (OMIM) Terms

NOTImmunodeficiency with Hyper-IgM, Type 1; HIGM1
Mammalian Phenotype Terms assigned by genotype

Cd40lgtm1Imx/Cd40lgtm1Imx

        involves: 129S2/SvPas * C57BL/6
  • reproductive system phenotype
  • *normal* reproductive system phenotype (MGI Ref ID J:21137)
    • homozygous females are viable and fertile
  • homeostasis/metabolism phenotype
  • abnormal blood coagulation (MGI Ref ID J:75152)
    • thrombi formed in response to FeCl3 injury are fragile and prone to rupture and to embolizing
    • smaller thrombi with lower platelet density
    • clotting times are normal
  • immune system phenotype
  • abnormal microglial cell physiology (MGI Ref ID J:115487)
    • increased microgliosis
  • increased susceptibility to prion infection (MGI Ref ID J:115487)
    • early onset of disease when infected with scrapie
    • succumb to infection after 144 days as opposed to 184 days for controls
    • symptoms of scrapie infection equivalent to 1000X higher dose
  • nervous system phenotype
  • abnormal nervous system physiology (MGI Ref ID J:115487)
    • abnormal microglial cell physiology (MGI Ref ID J:115487)
      • increased microgliosis
    • neurodegeneration (MGI Ref ID J:115487)
      • increased apoptosis
      • spongiform encephalopathy (MGI Ref ID J:115487)
        • vacuolation resulting from scrapie infection more pronounced than in controls
  • loss of cortex neurons (MGI Ref ID J:115487)
    • more severe loss of parvalbumin positive neurons in the cortex as a result of scrapie infection than occurs in controls

Cd40lgtm1Imx/Y

        involves: 129S2/SvPas * C57BL/6
  • immune system phenotype
  • *normal* immune system phenotype (MGI Ref ID J:21137)
    • serum IgM and IgG3 levels are more or less normal at all ages
    • abnormal immune system organ morphology (MGI Ref ID J:21137)
      • abnormal lymph node morphology (MGI Ref ID J:21137)
        • abnormal lymph node cellularity (MGI Ref ID J:21137)
          • about 1/3 that of controls while overall T and B cell numbers are normal
        • absent lymph node germinal center (MGI Ref ID J:21137)
          • failure to form germinal centers in inguinal lymph nodes although primary follicle formation is normal
      • absent spleen germinal center (MGI Ref ID J:21137)
        • failure to form germinal centers
    • abnormal immune system physiology (MGI Ref ID J:21137)
      • abnormal antigen presentation (MGI Ref ID J:21137)
        • unable to mount a secondary response to TNP-KLH antigen (T cell dependent)
        • T cell independent responses are normal as is isotype switching for these antigens
      • abnormal class switch recombination (MGI Ref ID J:21137)
      • decreased immunoglobulin level (MGI Ref ID J:21137)
        • decreased IgA level (MGI Ref ID J:21137)
        • decreased IgE level (MGI Ref ID J:21137)
          • undetectable
        • decreased IgG1 level (MGI Ref ID J:21137)
        • decreased IgG2b level (MGI Ref ID J:21137)
  • hematopoietic system phenotype
  • abnormal class switch recombination (MGI Ref ID J:21137)
  • absent spleen germinal center (MGI Ref ID J:21137)
    • failure to form germinal centers

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Cd40lgtm1Imx/Cd40lgtm1Imx

        involves: 129S2/SvPas * C57BL/6J * BALB/c
  • immune system phenotype
  • abnormal T cell clonal deletion (MGI Ref ID J:110925)
    • mice show complete rescue of CD8+ and CD4+ V beta11+ and beta6+ bearing CD4+ and CD8+ thymocytes from deletion in the thymus and periphery and Vbeta5+ CD4+ cells, but not Vbeta5+ bearing CD8+ thymocytes
  • hematopoietic system phenotype
  • abnormal T cell clonal deletion (MGI Ref ID J:110925)
    • mice show complete rescue of CD8+ and CD4+ V beta11+ and beta6+ bearing CD4+ and CD8+ thymocytes from deletion in the thymus and periphery and Vbeta5+ CD4+ cells, but not Vbeta5+ bearing CD8+ thymocytes

Cd40lgtm1Imx/Cd40lgtm1Imx

        B6.129S2-Cd40lgtm1Imx/J
  • nervous system phenotype
  • abnormal thalamus morphology (MGI Ref ID J:106362)
    • loss of neurons in the submedial thalamic nucleus due to thiamine deficiency slower than in controls
    • after 11 days of thiamine deficiency, neuron loss in the submedial thalamic nucleus due to thiamine deficiency is about 90%

Gene & Allele Details

Allele Symbol Cd40lgtm1Imx
Allele Name targeted mutation 1, Immunex
Common Name(s) CD154-; CD40L-; CD40LKO; Tnfsf5tm1Imx;
Mutation Made By Jacques Peschon,   Amgen
Strain of Origin129S2/SvPas
ES Cell Line NameD3
ES Cell Line Strain129S2/SvPas
Gene Symbol and Name Cd40lg, CD40 ligand
Chromosome X
Gene Common Name(s) CD154; CD40 antigen ligand; CD40L; Cd40l; HIGM1; IGM; IMD3; Ly-62; Ly62; T-BAM; TNFSF5; TRAP; Tnfsf5; gp39; hCD40L; lymphocyte antigen 62; tumor necrosis factor (ligand) superfamily, member 5;
Molecular Note Exons 3 and 4 were deleted by the insertion of a neomycin cassette. Homozygous mutant animals fail to express functional protein on the cell surface. [MGI Ref ID J:21137]

Control Information

  Allele   Control
 Cd40lgtm1Imx  101045 B6129SF2/J (approximate)
 
  Considerations for Choosing Controls

Genotyping Protocols

Cd40lgtm1Imx

Colony Maintenance

Breeding & HusbandryThese mutant mice (male hemizygotes and female homozygotes) are fertile. Sex ratios among offspring were normal. The mice are maintained as C57BL/6 X 129 hybrids. They are also being backcrossed onto a C57BL/6 background. Expected coat colors from breeding:Black and White Bellied Agouti
Diet Information LabDiet® 5K52/5K67

Related Strains

Strains carrying   Cd40lgtm1Imx allele
002770   B6.129S2-Cd40lgtm1Imx/J
View Strains carrying   Cd40lgtm1Imx     (1 strain)

Research Applications

This mouse can be used to support research in many areas including:

Cd40lgtm1Imx related

Cancer Research
Genes Regulating Growth and Proliferation

Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers

Mouse/Human Gene Homologs
immunodeficiency with hyper-IgM, type I (hyper-IgM syndrome)

References

Selected Reference(s)

Renshaw BR; Fanslow WC 3rd; Armitage RJ; Campbell KA; Liggitt D; Wright B; Davison BL; Maliszewski CR. 1994. Humoral immune responses in CD40 ligand-deficient mice. J Exp Med 180(5):1889-900. [PubMed: 7964465]  [MGI Ref ID J:21137]

Additional References

Price and Supply Information

Strain Name: B6;129S2-Cd40lgtm1Imx/J
Stock Number: 002428

Price Details

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Supply Details

Standard SupplyRepository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.
Supply Notes Cryorecovery - Standard.
The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services: Tel: 1-800-422-6423 or 1-207-288-5845; Email: jaxservices@jax.org.
This strain is included in the Induced Mutant Resource Colony collection.
Genomic DNA is available for this strain from the Mouse DNA Resource.

LicensingSee General Terms and Conditions below  
Control InformationView Control Information in Strain Details.

General Terms and Conditions

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.
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