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Strain Name:

B6;129S2-Ltatm1Dch/J

Stock Number:

002257

Availability:

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Genes & Alleles   Lta;   Ltatm1Dch;

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 David Chaplin,   University of Alabama at Birmingham
GenerationF?+4

Appearance
white-bellied agouti
Related Genotype: Aw/?

black
Related Genotype: a/a

Strain Description
Mice homozygous Ltatm1Dch targeted mutation are viable and fertile. Homozygous mutant mice show abnormal development of peripheral lymphoid organs with no detectable popliteal, inguinal, para-aortic, mesenteric, axillary, or cervical lymph nodes, and no detectable Peyer's patches. Morphological changes in the spleen white pulp were accompanied by alterations in T and B cell content. CD4+ and CD8+ T cells counts in peripheral blood are normal but there is a four-fold increase in B cells. Neutrophil, monocyte, and platelet counts are normal. The thymus contains normal numbers of CD4+CD8+, CD4+, CD8+, and CD4-CD8- T cells. Splenic T cells develop normal MHC class I and class II-restricted allocytotoxic responses. Also known as tumor necrosis factor beta, Tnfb.

Strain Development
The targeting strategy resulted in the elemination of exon 3 (4 exons total) and the introduction of a stop codon in exon 2. The predominant 1.5 and 1.8 kb Lta transcripts are missing and a major 3 kb transcript consistent with the structure of the targeted gene is present. 129 derived D3 ES cells were used for the targeting

Mammalian Phenotype Terms assigned by genotype

Ltatm1Dch/Ltatm1Dch

        involves: 129S2/SvPas * C57BL/6
  • life span-post-weaning/aging
  • abnormal induced morbidity/mortality (MGI Ref ID J:109621)
    • in response to LPS and D-GalN administration, percentage of severely moribund mice is 0 at 7 hours; 3/7 mice are severely moribund at 8 hours
  • immune system phenotype
  • abnormal class switch recombination (MGI Ref ID J:109621)
    • 19 days after immunization with OVA, mice display an isotype switch to IgG from IgM that is several fold decreased compared to wild type
  • abnormal humoral immune response (MGI Ref ID J:39746)
    • in response to stimulation with sheep red blood cells (SRBC), mice fail to produce anti-SRBC IgG at day 6 and only produce a negligible amount by day 15 unlike wild type mice
  • abnormal leukocyte cell number (MGI Ref ID J:17976)
    • decreased T cell number (MGI Ref ID J:17976)
      • in the spleen
    • increased leukocyte cell number (MGI Ref ID J:17976)
      • nearly 3 fold increase
      • neutrophil, monocyte, platelet counts normal
      • increased B cell number (MGI Ref ID J:17976)
        • 4 fold increase in B cell numbers
        • 30% increase in IgM positive and B220 positive B lymphocytes
  • abnormal lymph node morphology (MGI Ref ID J:17976)
    • lack para-aortic lymph nodes
    • abnormal axillary lymph node morphology (MGI Ref ID J:17976)
      • absent
    • abnormal cervical lymph node morphology (MGI Ref ID J:17976)
      • absent
    • abnormal inguinal lymph node morphology (MGI Ref ID J:17976)
      • absent
    • abnormal lymph node primary follicle (MGI Ref ID J:109621)
      • only occasional BP-3 cells are found in some lymphoid follicles
    • abnormal popliteal lymph node morphology (MGI Ref ID J:17976)
      • absent
    • absent mesenteric lymph nodes (MGI Ref ID J:17976)
      • mice lack mesenteric and cervical lymph nodes
  • abnormal spleen morphology (MGI Ref ID J:17976)
    • mice exhibit extensive disorganization
    • abnormal spleen periarteriolar lymphoid sheath morphology (MGI Ref ID J:17976)
    • absent spleen marginal zone (MGI Ref ID J:17976)
      • loss of a distinct marginal zone
    • decreased spleen white pulp amount (MGI Ref ID J:109621)
      • percentage of splenic white pulp is lower than in wild type, Ltb nulls and Ltatm1.1Sned but higher than Ltb, Ltbr or Ltb/Tnf/Lta knockouts
  • absent Peyer's patches (MGI Ref ID J:17976)
    • not grossly detectable
  • decreased interferon-gamma secretion (MGI Ref ID J:109621)
    • in culture, OVA-specific Ifng production from purified CD4+ T cells is decreased 2-fold compared to Ltatm1.1Sned
  • decreased tumor necrosis factor secretion (MGI Ref ID J:109621)
    • in response to LPS, mice demonstrate a 10-fold decrease in production of TNF compared to wild type or Lta
    • both bone marrow derived macrophages and neutrophils fail to produce normal levels of TNF when stimulated
  • hematopoietic system phenotype
  • abnormal class switch recombination (MGI Ref ID J:109621)
    • 19 days after immunization with OVA, mice display an isotype switch to IgG from IgM that is several fold decreased compared to wild type
  • abnormal leukocyte cell number (MGI Ref ID J:17976)
    • decreased T cell number (MGI Ref ID J:17976)
      • in the spleen
    • increased leukocyte cell number (MGI Ref ID J:17976)
      • nearly 3 fold increase
      • neutrophil, monocyte, platelet counts normal
      • increased B cell number (MGI Ref ID J:17976)
        • 4 fold increase in B cell numbers
        • 30% increase in IgM positive and B220 positive B lymphocytes
  • abnormal spleen morphology (MGI Ref ID J:17976)
    • mice exhibit extensive disorganization
    • abnormal spleen periarteriolar lymphoid sheath morphology (MGI Ref ID J:17976)
    • absent spleen marginal zone (MGI Ref ID J:17976)
      • loss of a distinct marginal zone
    • decreased spleen white pulp amount (MGI Ref ID J:109621)
      • percentage of splenic white pulp is lower than in wild type, Ltb nulls and Ltatm1.1Sned but higher than Ltb, Ltbr or Ltb/Tnf/Lta knockouts

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

Ltatm1Dch/Ltatm1Dch

        B6.129S2-Ltatm1Dch
  • immune system phenotype
  • abnormal immune serum protein physiology (MGI Ref ID J:80616)
    • abnormal cytokine secretion (MGI Ref ID J:95222)
      • chemokine expression is essentially absent
      • no Ifn-gamma produced in nasal-associated lymphoid tissue but it is found in the spleen
    • decreased IgG level (MGI Ref ID J:80616)
      • defecient IgG antibody production
    • increased IgM level (MGI Ref ID J:80616)
      • 2-fold increased IgM
  • abnormal mucosa-associated lymphoid tissue morphology (MGI Ref ID J:80616)
    • nasal-associated lymphoid tissue poorly developed and hypocellular
  • absent Peyer's patches (MGI Ref ID J:80616)
    • not grossly detectable
  • absent spleen germinal center (MGI Ref ID J:80616)
  • absent spleen marginal zone (MGI Ref ID J:80616)
  • decreased spleen white pulp amount (MGI Ref ID J:80616)
  • increased leukocyte cell number (MGI Ref ID J:80616)
    • 2- to 3- fold increased leukocyte count in spleen, blood, and peritoneal cavity
  • hematopoietic system phenotype
  • absent spleen germinal center (MGI Ref ID J:80616)
  • absent spleen marginal zone (MGI Ref ID J:80616)
  • decreased spleen white pulp amount (MGI Ref ID J:80616)
  • increased leukocyte cell number (MGI Ref ID J:80616)
    • 2- to 3- fold increased leukocyte count in spleen, blood, and peritoneal cavity

Ltatm1Dch/Ltatm1Dch

        B6.129S2-Ltatm1Dch/J
  • immune system phenotype
  • abnormal lymph organ development (MGI Ref ID J:73100)

Gene & Allele Details

Allele Symbol Ltatm1Dch
Allele Name targeted mutation 1, David D Chaplin
Common Name(s) LT-; LT-alpha-; LTalpha-;
Mutation Made By David Chaplin,   University of Alabama at Birmingham
Strain of Origin129S2/SvPas
ES Cell Line NameD3
ES Cell Line Strain129S2/SvPas
Gene Symbol and Name Lta, lymphotoxin A
Chromosome 17
Gene Common Name(s) LT; LT-[a]; LT-alpha; LT[a]; LTalpha; Ltx; TNF beta; TNF-beta; TNFB; TNFSF1; Tnfb; Tnfsf1b; heart, lung and blood 382; hlb382; lymphotoxin; lymphotoxin alpha; tumor necrosis factor beta;
Molecular Note A neomycin resistance cassette replaced a small portion of exon 2, all of exon 3, and a small portion of exon 4. [MGI Ref ID J:110548] [MGI Ref ID J:17976] [MGI Ref ID J:95222]

Control Information

  Allele   Control
 Ltatm1Dch  101045 B6129SF2/J (approximate)
 
  Considerations for Choosing Controls

Genotyping Protocols

Ltatm1Dch

Colony Maintenance

Breeding & HusbandryThis strain is currently maintained by homozygous sibling matings. Expected coat color from breeding:White Bellied Agouti and Black
Diet Information LabDiet® 5K52/5K67

Related Strains

Strains carrying   Ltatm1Dch allele
002258   B6.129S2-Ltatm1Dch/J
View Strains carrying   Ltatm1Dch     (1 strain)

Strains carrying other alleles of Lta
005108   B6.129P2-Ltb/Tnf/Ltatm1Dvk/J
005579   C57BL/6J-Ltahlb382/J
View Strains carrying other alleles of Lta     (2 strains)

Research Applications

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

Ltatm1Dch related

Cancer Research
Growth Factors/Receptors/Cytokines

Immunology and Inflammation Research
Growth Factors/Receptors/Cytokines

References

Selected Reference(s)

De Togni P; Goellner J; Ruddle NH; Streeter PR; Fick A; Mariathasan S; Smith SC; Carlson R; Shornick LP; Strauss-Schoenberger J; Russell JH; Karr R; Chaplin DD. 1994. Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin [see comments] Science 264(5159):703-7. [PubMed: 8171322]  [MGI Ref ID J:17976]

Additional References

Price and Supply Information

Strain Name: B6;129S2-Ltatm1Dch/J
Stock Number: 002257

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 for Licensing and Use Restrictions  
Control InformationView Control Information in Strain Details.

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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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