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.

Genetics

Lta^hlb382

Allele Symbol: Lta^hlb382

Allele Name	heart, lung and blood 382
Allele Type	Chemically induced (ENU)
Allele Synonym(s)
Gene Symbol and Name	Lta, lymphotoxin A
Gene Synonym(s)
Strain of Origin	C57BL/6J
Chromosome	17
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.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Lta^hlb382 related

Hematological Research
- Immunological Defects

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Lta^hlb382/Lta^hlb382
C57BL/6J-Lta/J

immune system phenotype

decreased transitional stage B cell number
- the absolute numbers of transitional B cells are moderately reduced

increased leukocyte cell number
- increased white blood count on non-fasted whole blood analysis (WBC = 15.39 x 10^3 cells per microliter)

absent spleen germinal center
- germinal centers are absent from the spleen

abnormal immune system organ morphology

lung inflammation
- small clusters of lymphocytes are observed in the lungs of mice

absent lymph nodes
- mice lack all peripheral and mesenteric lymph nodes and contain no peyer's patches

increased B-1b cell number
- the percentage of B1-b cells in the peritoneum is more than 2-fold higher than in wild-type controls
- there is a dramatic increase in the absolute numbers of B1b cells found in the peritoneum compared to wild-type

absent marginal zone B cells
- there are no marginal zone B cells found in the spleen

absent mesenteric lymph nodes
- mice lack all mesenteric lymph nodes

absent Peyer's patches
- Peyer's patches are absent in these mice

absent spleen marginal zone
- the marginal zone is absent in the spleen along with having poorly defined T cells and B cell zones

decreased NK cell number
- the number of NK cells found in the spleen is reduced by 62% compared to wild-type mice

liver inflammation
- small clusters of lymphocytes are observed in the livers of mice

hematopoietic system phenotype

absent spleen germinal center
- germinal centers are absent from the spleen

increased leukocyte cell number
- increased white blood count on non-fasted whole blood analysis (WBC = 15.39 x 10^3 cells per microliter)

increased B-1b cell number
- the percentage of B1-b cells in the peritoneum is more than 2-fold higher than in wild-type controls
- there is a dramatic increase in the absolute numbers of B1b cells found in the peritoneum compared to wild-type

absent marginal zone B cells
- there are no marginal zone B cells found in the spleen

decreased NK cell number
- the number of NK cells found in the spleen is reduced by 62% compared to wild-type mice

absent spleen marginal zone
- the marginal zone is absent in the spleen along with having poorly defined T cells and B cell zones

decreased transitional stage B cell number
- the absolute numbers of transitional B cells are moderately reduced

liver/biliary system phenotype

liver inflammation
- small clusters of lymphocytes are observed in the livers of mice

respiratory system phenotype

lung inflammation
- small clusters of lymphocytes are observed in the lungs of mice

References

Additional - Lta^hlb382 related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Sanger sequencing:Lta
- Genotyping resources and troubleshooting
Citation
When using the C57BL/6J-Lta^hlb382/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #005579 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Homozygous forLta<hlb382> , 1 pair minimum

Related Products and Services

Frozen Mouse Embryo	C57BL/6J-Lta<hlb382>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	C57BL/6J-Lta<hlb382>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	C57BL/6J-Lta<hlb382>/J Frozen Embryos	$3373.50
Frozen Mouse Embryo	C57BL/6J-Lta<hlb382>/J Frozen Embryos	$3373.50

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The Jackson Laboratory's Genotype Promise

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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Also Known As:HLB-382, HLB382

Genetic overview

Research Applications

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Detailed Description