Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names C57BL/6J-Ltahlb382    (Changed: 10-JUN-08 ) C57BL/6J-hlb382/J    (Changed: 10-JUN-08 ) Type Chemically Induced Mutation; Coisogenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse H2 Haplotype b Generation ?+F1p Generation Definitions

Description
Mice that are homozygous for the mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Screening of third generation mice (G3)identified a non-fasted female (born 10/9/2003) with an increased white blood cell count of 15.39 x 103 cells/ul, which is approximately 92% higher than controls. This mutant mouse strain may be useful in studies of leukocytosis.

Development
Following multidose ethylnitrosourea (ENU) treatments to induce mutations in male founder C57BL/6J mice (Stock No. 000664), a forward genetic screen was utilized to identify phenotypic deviants in complex heart, lung, blood, and sleep disorders, at the Mouse Heart, Lung, Blood, and Sleep Disorders (HLBS) Center at The Jackson Laboratory. The phenotype was mapped to chromosome 17. Sequencing of the candidate gene Lta, lymphotoxin A, revealed an insertion of a cytosine occurred between nucleotides 16 and 17 of the second exon. This is predicted to cause a frameshift mutation from amino acid 6 and translation of a theoretical new peptide of 173 amino acids with a premature stop codon in exon 4. Heterozygotes were crossed to generate homozygotes. The mice have been maintained on a C57BL/6J background.

Related Strains

Strains carrying other alleles of Lta

005108	B6.129P2-Ltb/Tnf/Ltatm1Dvk/J
002258	B6.129S2-Ltatm1Dch/J
002257	B6;129S2-Ltatm1Dch/J

View Strains carrying other alleles of Lta     (3 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Lta^hlb382/Lta^hlb382

        C57BL/6J-Lta^hlb382/J

• immune system phenotype
• abnormal immune system organ morphology   (MGI Ref ID J:134498)
• • absent Peyer's patches
    • Peyer's patches are absent in these mice   (MGI Ref ID J:134498)
  • absent lymph nodes
    • mice lack all peripheral and mesenteric lymph nodes and contain no peyer's patches   (MGI Ref ID J:134498)
  • absent marginal zone B cells
    • there are no marginal zone B cells found in the spleen   (MGI Ref ID J:134498)
  • absent mesenteric lymph nodes
    • mice lack all mesenteric lymph nodes   (MGI Ref ID J:134498)
  • absent spleen germinal center
    • germinal centers are absent from the spleen   (MGI Ref ID J:134498)
  • absent spleen marginal zone
    • the marginal zone is absent in the spleen along with having poorly defined T cells and B cell zones   (MGI Ref ID J:134498)
• decreased NK cell number
  • the number of NK cells found in the spleen is reduced by 62% compared to wild-type mice   (MGI Ref ID J:134498)
• decreased transitional stage B cell number
  • the absolute numbers of transitional B cells are moderately reduced   (MGI Ref ID J:134498)
• increased leukocyte cell number
  • increased white blood count on non-fasted whole blood analysis (WBC = 15.39 x 10^3 cells per microliter)   (MGI Ref ID J:82961)
• • increased B-1b cell number
    • there is a dramatic increase in the absolute numbers of B1b cells found in the peritoneum compared to wild-type   (MGI Ref ID J:134498)
    • the percentage of B1-b cells in the peritoneum is more than 2-fold higher than in wild-type controls   (MGI Ref ID J:134498)
• liver inflammation
  • small clusters of lymphocytes are observed in the livers of mice   (MGI Ref ID J:134498)
• lung inflammation
  • small clusters of lymphocytes are observed in the lungs of mice   (MGI Ref ID J:134498)
• hematopoietic system phenotype
• absent marginal zone B cells
  • there are no marginal zone B cells found in the spleen   (MGI Ref ID J:134498)
• absent spleen germinal center
  • germinal centers are absent from the spleen   (MGI Ref ID J:134498)
• absent spleen marginal zone
  • the marginal zone is absent in the spleen along with having poorly defined T cells and B cell zones   (MGI Ref ID J:134498)
• decreased NK cell number
  • the number of NK cells found in the spleen is reduced by 62% compared to wild-type mice   (MGI Ref ID J:134498)
• decreased transitional stage B cell number
  • the absolute numbers of transitional B cells are moderately reduced   (MGI Ref ID J:134498)
• increased leukocyte cell number
  • increased white blood count on non-fasted whole blood analysis (WBC = 15.39 x 10^3 cells per microliter)   (MGI Ref ID J:82961)
• • increased B-1b cell number
    • there is a dramatic increase in the absolute numbers of B1b cells found in the peritoneum compared to wild-type   (MGI Ref ID J:134498)
    • the percentage of B1-b cells in the peritoneum is more than 2-fold higher than in wild-type controls   (MGI Ref ID J:134498)
• liver/biliary system phenotype
• liver inflammation
  • small clusters of lymphocytes are observed in the livers of mice   (MGI Ref ID J:134498)
• respiratory system phenotype
• lung inflammation
  • small clusters of lymphocytes are observed in the lungs of mice   (MGI Ref ID J:134498)
• cellular phenotype
• decreased transitional stage B cell number
  • the absolute numbers of transitional B cells are moderately reduced   (MGI Ref ID J:134498)

View Research Applications

Research Applications

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

Lta^hlb382 related

Hematological Research
Immunological Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Ltahlb382
Allele Name		heart, lung and blood 382
Allele Type		Chemically induced (ENU)
Strain of Origin		C57BL/6J
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		This phenotypic mutant was identified in an ENU mutagenesis screen. An insertion of a cytosine occurred between nucleotides 16 and 17 of the second exon. This is predicted to cause a frameshift mutation from amino acid 6 and translation of a theoretical new peptide of 173 amino acids with a premature stop codon in exon 4. Because Ltb and Tnf are found in nearby genomic locations, their sequence and expression were analyzed and found to be normal. Intra-cell flow cytometry failed to detect any Lta expression in activated B-cells.

Genotyping

Genotyping Information

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Lta^hlb382 related

JAX National Heart, Lung and Blood Program for Genomic Applications (PGA). 2003. Heritable mouse mutants from the JAX NHLBI ENU Mutagenesis Program MGI Direct Data Submission :.  [MGI Ref ID J:82961]

Wang H; Feng J; Qi C; Morse HC 3rd. 2008. An ENU-induced mutation in the lymphotoxin alpha gene impairs organogenesis of lymphoid tissues in C57BL/6 mice. Biochem Biophys Res Commun 370(3):461-7. [PubMed: 18384745]  [MGI Ref ID J:134498]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

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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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