Phenotypes associated with this allele

• Allele Symbol: Dgkz^tm1Gak
• Allele Name: targeted mutation 1, Gary A Koretzky
• Allele ID: MGI:2674915
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Dgkz^tm1Gak/Dgkz^tm1Gak	B6.129X1-Dgkz^tm1Gak	MGI:3689990
hm2	Dgkz^tm1Gak/Dgkz^tm1Gak	involves: 129X1/SvJ * C57BL/6	MGI:2674917
cx3	Dgka^tm1Xpz/Dgka^tm1Xpz Dgkz^tm1Gak/Dgkz^tm1Gak	involves: 129 * 129X1/SvJ * C57BL/6	MGI:3689991

Genotype
MGI:3689990

hm1

• Allelic Composition: Dgkz^tm1Gak/Dgkz^tm1Gak
• Genetic Background: B6.129X1-Dgkz^tm1Gak

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

immune system

increased T cell number ( J:113564 )

• stimulation of CD8+ T cell-depleted splenocyte cultures in which Dgka production is inhibited results in 2-3 rounds of proliferation in mutant T cells; mutant T cells grow and divide like wild-type T cells that receive CD28 costimulation

abnormal interleukin-2 secretion ( J:113564 )

• after stimulation with anti-CD3 and CTLA-4, wild-type T cells become anergic and produce very little IL-2, but mutant cells produce more IL-2; treatment of mutant cells with Dgka inhibitor results in levels of IL-2 production similar to those in anti-CD3-treated wild-type cells receiving CD28 costimulation

abnormal lymphocyte anergy ( J:113564 )

• treatment with anti-CD3 and anti-CD28 which induces anergy in wild-type T cells does not affect mutant T cells which can still grow and produce IL-2

hematopoietic system

increased T cell number ( J:113564 )

• stimulation of CD8+ T cell-depleted splenocyte cultures in which Dgka production is inhibited results in 2-3 rounds of proliferation in mutant T cells; mutant T cells grow and divide like wild-type T cells that receive CD28 costimulation

Genotype
MGI:2674917

hm2

• Allelic Composition: Dgkz^tm1Gak/Dgkz^tm1Gak
• Genetic Background: involves: 129X1/SvJ * C57BL/6

cellular

increased T cell proliferation ( J:85149 )

• T cells are hyperresponsive to TCR stimulation

skeleton

decreased susceptibility to induced arthritis ( J:293120 )

• mice injected with streptococcal cell wall (SCW) fragments in the ankle to induce a local inflammatory response are protected from SCW-induced arthritis, showing less swelling and despite the presence of inflammatory infiltrate, protection from joint and cartilage disruption

immune system

increased B cell number ( J:85149 )

• spleen and lymph nodes show a compensatory increase of B220+ B cells to the decrease in T cells

decreased CD4-positive, alpha-beta T cell number ( J:85149 )

• spleen and lymph nodes show a 5-10% decrease of Thy1+ cells in both CD4+ and CD8+ compartments, however CD4+ T cell levels are normal in the thymus

decreased CD8-positive, alpha-beta T cell number ( J:85149 )

• spleen and lymph nodes show a 5-10% decrease of Thy1+ cells in both CD4+ and CD8+ compartments, however CD8+ T cell numbers are normal in the thymus

abnormal T cell physiology ( J:85149 )

• TCR-induced phosphatidic acid production by T cells is inhibited compared with that of wild-type

abnormal T cell activation ( J:85149 )

• mice infected with lymphocytic chriomeningitis virus (LCMV) show a greater increase in total splenic CD8+ cells and a higher percentage of CD8+ cells with an activated phenotype 7 days after infection

increased T cell proliferation ( J:85149 )

• T cells are hyperresponsive to TCR stimulation

abnormal macrophage physiology ( J:293120 )

• marker analysis indicates that bone marrow macrophages exhibit impaired M1 macrophage polarization

abnormal cytokine level ( J:293120 )

• SCW-treated mice to induce arthritis show lower expression levels of proinflammatory cytokines IL-6, TNF-alpha, and IL-1beta

• CpG-administered mice to induce cytokine storm syndrome show lower IL-1beta, IL-6, and TNF-alpha mRNA levels in the liver

• bone marrow macrophages stimulated with LPS (a TLR4 ligand) or upon TLR3 activation with Poly(I:C) or TLR2 activation with Pam3CSK4 show reduced transcript levels of IL-6, TNF-alpha, and IL-1beta

abnormal interferon level ( J:85149 )

• a higher percentage of lymphocytic chriomeningitis virus-specific CD8+ T cells stimulated with major histocompatibility complex class I-specific peptide NP396 or the major histocompatibility complex class II-specific peptide GP61 express interferon-gamma than wild-type T cells

abnormal cytokine secretion ( J:293120 )

• bone marrow macrophages stimulated with LPS, Pam3CSK4, or CpG secrete lower levels of proinflammatory cytokines

decreased interleukin-6 secretion ( J:293120 )

• CpG-administered mice show decreased IL-6 serum levels compared to wild-type mice

abnormal inflammatory response ( J:293120 )

• mice administered the TLR9 ligand CpG to induce cytokine storm syndrome show a similar increase in spleen and liver weight, decrease in WBC counts, areas of inflammatory infiltrates in the liver and percentage of F4/80+CD11b+ liver macrophages as in controls indicting that tissue infiltration by monocytes/macrophages is not affected, however serum ferritin levels are lower and production of inflammatory cytokines is reduced

decreased susceptibility to induced arthritis ( J:293120 )

• mice injected with streptococcal cell wall (SCW) fragments in the ankle to induce a local inflammatory response are protected from SCW-induced arthritis, showing less swelling and despite the presence of inflammatory infiltrate, protection from joint and cartilage disruption

decreased susceptibility to Riboviria infection ( J:85149 )

• immune response to lymphocytic choriomeningitis virus infection is more robust than that observed in wild-type and mutants show a 50-70% reduction in viral titeres

hematopoietic system

increased B cell number ( J:85149 )

• spleen and lymph nodes show a compensatory increase of B220+ B cells to the decrease in T cells

decreased CD4-positive, alpha-beta T cell number ( J:85149 )

• spleen and lymph nodes show a 5-10% decrease of Thy1+ cells in both CD4+ and CD8+ compartments, however CD4+ T cell levels are normal in the thymus

decreased CD8-positive, alpha-beta T cell number ( J:85149 )

• spleen and lymph nodes show a 5-10% decrease of Thy1+ cells in both CD4+ and CD8+ compartments, however CD8+ T cell numbers are normal in the thymus

abnormal T cell physiology ( J:85149 )

• TCR-induced phosphatidic acid production by T cells is inhibited compared with that of wild-type

abnormal T cell activation ( J:85149 )

• mice infected with lymphocytic chriomeningitis virus (LCMV) show a greater increase in total splenic CD8+ cells and a higher percentage of CD8+ cells with an activated phenotype 7 days after infection

increased T cell proliferation ( J:85149 )

• T cells are hyperresponsive to TCR stimulation

abnormal macrophage physiology ( J:293120 )

• marker analysis indicates that bone marrow macrophages exhibit impaired M1 macrophage polarization

homeostasis/metabolism

decreased circulating ferritin level ( J:293120 )

• mice administered the TLR9 ligand CpG to induce cytokine storm syndrome show lower serum ferritin levels

abnormal cytokine level ( J:293120 )

• SCW-treated mice to induce arthritis show lower expression levels of proinflammatory cytokines IL-6, TNF-alpha, and IL-1beta

• CpG-administered mice to induce cytokine storm syndrome show lower IL-1beta, IL-6, and TNF-alpha mRNA levels in the liver

• bone marrow macrophages stimulated with LPS (a TLR4 ligand) or upon TLR3 activation with Poly(I:C) or TLR2 activation with Pam3CSK4 show reduced transcript levels of IL-6, TNF-alpha, and IL-1beta

abnormal interferon level ( J:85149 )

• a higher percentage of lymphocytic chriomeningitis virus-specific CD8+ T cells stimulated with major histocompatibility complex class I-specific peptide NP396 or the major histocompatibility complex class II-specific peptide GP61 express interferon-gamma than wild-type T cells

Genotype
MGI:3689991

cx3

• Allelic Composition: Dgka^tm1Xpz/Dgka^tm1Xpz; Dgkz^tm1Gak/Dgkz^tm1Gak
• Genetic Background: involves: 129 * 129X1/SvJ * C57BL/6

hematopoietic system

abnormal thymocyte activation ( J:113564 )

• the few T cells present diplay constitutive expression of activation markers indicating inappropriate activation

abnormal T cell differentiation ( J:113564 )

• double mutants have substantial defects in thymocyte development; few CD4+ and CD8+ thymocytes and peripheral T cells are detected

immune system

abnormal thymocyte activation ( J:113564 )

• the few T cells present diplay constitutive expression of activation markers indicating inappropriate activation

abnormal T cell differentiation ( J:113564 )

• double mutants have substantial defects in thymocyte development; few CD4+ and CD8+ thymocytes and peripheral T cells are detected

endocrine/exocrine glands

abnormal thymocyte activation ( J:113564 )

• the few T cells present diplay constitutive expression of activation markers indicating inappropriate activation