These Dgkz knockout mice exhibit a 5-10% decrease of CD4+ and CD8+ T cells and an increase of B220+ B cells in spleen and lymph nodes, with normal CD4+ T cell numbers in the thymus. They may be useful for studying the role of diacylglycerol in T cell development and function.
Gary Koretzky, University of Pennsylvania
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Reporter, Null/Knockout) | Dgkz | diacylglycerol kinase zeta |
An internal ribosome entry site (IRES)-GFP followed by a loxP-flanked neomycin resistance cassette replaces the C1 and kinase domains of the diacylglycerol kinase zeta (Dgkz) gene, abolishing gene function. DGKζ is an enzyme expressed in T cells, B cells, mast cells, neutrophils, macrophages, and dendritic cells as well as many other non-hematopoietic cells. DGKζ converts diacylglycerol, a compound essential to normal T cell homeostasis, to phosphatidic acid which has been found to inhibit TCR signaling. These mice have a 5-10% decrease of CD4+ and CD8+ T cells and an increase of B220+ B cells in spleen and lymph nodes, with normal CD4+ T cell numbers in the thymus. T cells of DGKζ-deficient mice are hyper-responsive to TCR stimulation, and show enhanced activation of the Ras-ERK cascade and increased expression of activation markers. These mice exhibit an increase in total splenic CD8+ cells in response to viral infection. Homozygotes are viable and fertile.
A targeting vector was designed to replace exons encoding the C1 and kinase domains of the diacylglycerol kinase zeta (Tsc22d1) gene with an internal ribosome entry site (IRES)-GFP followed by a loxP-flanked neomycin resistance cassette. The construct was electroporated into 129X1/SvJ-derived RW4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and the resulting chimeric mice were bred to C57BL/6J mice to generate the mutant colony. These mutant mice were bred to C57BL/6J mice for at least 9 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.
Expressed Gene | GFP, Green Fluorescent Protein, |
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Site of Expression | The diacylglycerol kinase zeta (Dgkz) gene is normally expressed in T cells, B cells, mast cells, neutrophils, macrophages, and dendritic cells as well as many other non-hematopoietic cells. |
Allele Name | targeted mutation 1, Gary A Koretzky |
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Allele Type | Targeted (Reporter, Null/Knockout) |
Allele Synonym(s) | Dgkz-; Dgkzeta-; Dgkzeta KO |
Gene Symbol and Name | Dgkz, diacylglycerol kinase zeta |
Gene Synonym(s) | |
Expressed Gene | GFP, Green Fluorescent Protein, |
Site of Expression | The diacylglycerol kinase zeta (Dgkz) gene is normally expressed in T cells, B cells, mast cells, neutrophils, macrophages, and dendritic cells as well as many other non-hematopoietic cells. |
Strain of Origin | 129X1/SvJ |
Chromosome | 2 |
Molecular Note | A cassette containing floxed neo and IRES-GFP replaced 6.1 kb of genomic sequence encompassing exons encoding the C1 and kinase domains. Normal protein was undetected by Western blot analysis of homozygous mutant thymocytes, splencytes, and bone marrow-derived macrophages. |
Mutations Made By | Gary Koretzky, University of Pennsylvania |
When maintaining a live colony, homozygous mice may be bred together.
When using the B6.129X1-Dgkztm1Gak/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #018861 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Dgkz<tm1Gak> |
Frozen Mouse Embryo | B6.129X1-Dgkz<tm1Gak>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129X1-Dgkz<tm1Gak>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129X1-Dgkz<tm1Gak>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6.129X1-Dgkz<tm1Gak>/J Frozen Embryo | $3373.50 |
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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. 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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