Phenotypes associated with this allele

• Allele Symbol: Mapkapk2^tm1Mgl
• Allele Name: targeted mutation 1, Matthias Gaestel
• Allele ID: MGI:2179724
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Mapkapk2^tm1Mgl/Mapkapk2^tm1Mgl	involves: 129P2/OlaHsd * 129S/SvEvBrd * C57BL/6	MGI:3698631
hm2	Mapkapk2^tm1Mgl/Mapkapk2^tm1Mgl	involves: 129P2/OlaHsd * C57BL/6J	MGI:2680288
hm3	Mapkapk2^tm1Mgl/Mapkapk2^tm1Mgl	involves: 129S * C57BL/6	MGI:2680290
cx4	Ldlr^tm1Her/Ldlr^tm1Her Mapkapk2^tm1Mgl/Mapkapk2^tm1Mgl	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6	MGI:4367112
cx5	Mapkapk2^tm1Mgl/Mapkapk2^tm1Mgl Mapkapk3^tm1.1Lex/Mapkapk3^tm1.1Lex	involves: 129P2/OlaHsd * 129S/SvEvBrd * C57BL/6	MGI:3698632
cx6	Mapkapk2^tm1Mgl/Mapkapk2^tm1Mgl Tnf^tm2Gkl/Tnf^+	involves: 129P2/OlaHsd * 129S/SvEv * C57BL/6J	MGI:3629603

Genotype
MGI:3698631

hm1

• Allelic Composition: Mapkapk2^tm1Mgl/Mapkapk2^tm1Mgl
• Genetic Background: involves: 129P2/OlaHsd * 129S/SvEvBrd * C57BL/6

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

immune system

abnormal cytokine secretion ( J:117668 )

• LPS-induced production of tristetraprolin and TNF is reduced compared to wild-type mice

Genotype
MGI:2680288

hm2

• Allelic Composition: Mapkapk2^tm1Mgl/Mapkapk2^tm1Mgl
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

immune system

abnormal macrophage derived foam cell morphology ( J:142788 )

• macrophage foam cell formation is significantly reduced after macrophage incubation with oxLDL

increased spleen germinal center size ( J:59678 )

• germinal centers are significantly enlarged compared to controls after immunization with TNP-KLH due to decreased apoptosis in the region

abnormal cytokine level ( J:59678 )

• LPS-induced TNF-alpha and IFN-gamma release is reduced in cultured spleen cells, however this is not due to reduced levels or stability of mRNA or impaired secretion but reduced post-transcriptional biosynthesis

• LPS-induced IL-1beta and IL-6 release is reduced in cultured spleen cells due to a reduction in mRNA levels

decreased circulating tumor necrosis factor level ( J:59678 )

• serum TNF-alpha levels are reduced by more than 90% following LPS challenge compared to controls

decreased susceptibility to endotoxin shock ( J:59678 )

• increased survival after LPS-induced endotoxic shock due to a drastic reduction of Tnf-alpha biosynthesis, not to impaired TNF receptor signaling

cardiovascular system

abnormal response to cardiac infarction ( J:101888 )

• homozygotes display no significant differences in baseline cardiac function relative to wild-type mice

• however, homozygotes are resistant to ischemic reperfusion myocardial injury, with a significantly enhanced post-ischemic recovery of left ventricular function relative to wild-type mice

decreased myocardial infarct size ( J:101888 )

• following ischemia-reperfusion myocardial injury, homozygotes exhibit a ~20% reduction in myocardial infarct size relative to non-preconditioned wild-type mice

muscle

decreased cardiomyocyte apoptosis ( J:101888 )

• following ischemia-reperfusion myocardial injury, homozygotes display a significant reduction in the number of apoptotic cardiomyocytes relative to wild-type mice

homeostasis/metabolism

abnormal response to cardiac infarction ( J:101888 )

• homozygotes display no significant differences in baseline cardiac function relative to wild-type mice

• however, homozygotes are resistant to ischemic reperfusion myocardial injury, with a significantly enhanced post-ischemic recovery of left ventricular function relative to wild-type mice

decreased myocardial infarct size ( J:101888 )

• following ischemia-reperfusion myocardial injury, homozygotes exhibit a ~20% reduction in myocardial infarct size relative to non-preconditioned wild-type mice

abnormal cytokine level ( J:59678 )

• LPS-induced TNF-alpha and IFN-gamma release is reduced in cultured spleen cells, however this is not due to reduced levels or stability of mRNA or impaired secretion but reduced post-transcriptional biosynthesis

• LPS-induced IL-1beta and IL-6 release is reduced in cultured spleen cells due to a reduction in mRNA levels

decreased circulating tumor necrosis factor level ( J:59678 )

• serum TNF-alpha levels are reduced by more than 90% following LPS challenge compared to controls

hematopoietic system

abnormal macrophage derived foam cell morphology ( J:142788 )

• macrophage foam cell formation is significantly reduced after macrophage incubation with oxLDL

increased spleen germinal center size ( J:59678 )

• germinal centers are significantly enlarged compared to controls after immunization with TNP-KLH due to decreased apoptosis in the region

cellular

abnormal macrophage derived foam cell morphology ( J:142788 )

• macrophage foam cell formation is significantly reduced after macrophage incubation with oxLDL

decreased cardiomyocyte apoptosis ( J:101888 )

• following ischemia-reperfusion myocardial injury, homozygotes display a significant reduction in the number of apoptotic cardiomyocytes relative to wild-type mice

Genotype
MGI:2680290

hm3

• Allelic Composition: Mapkapk2^tm1Mgl/Mapkapk2^tm1Mgl
• Genetic Background: involves: 129S * C57BL/6

mortality/aging

increased susceptibility to bacterial infection induced morbidity/mortality ( J:76161 )

• in response to i.v. injection with 1.5 x 10⁵ CFU/kg virulent L. monocytogenes, only 1 of 7 homozygotes (vs 9 of 10 wild-type controls) survive the 14-day observation period post-infection

• however, all homozygotes survive L. monocytogenes infection with 10⁴ CFU/kg

immune system

impaired macrophage phagocytosis ( J:76161 )

• in an optimized quantitative phagocytosis assay, mutant bone marrow-derived macrophages (BMDMs) display reduced uptake of rhodamine-labeled E. coli particles relative to wild-type BMDMs

• however, macrophage generation of NO and oxidative burst activity in response to L. monocytogenes are both normal

decreased interferon-gamma secretion ( J:76161 )

• in vitro, isolated spleen cells from homozygous mutant mice show strongly diminished IFN-gamma production in response to stimulation with heat-killed L. monocytogenes (HKLM)

increased interleukin-1 beta secretion ( J:76161 )

• in response to stimulation with HKLM, mutant BMDMs display an enhanced IL-1 beta release relative to similarly-treated wild-type BMDMs

decreased tumor necrosis factor secretion ( J:76161 )

• at 72 hrs post-infection with 1.5 x 10⁵ CFU/kg virulent L. monocytogenes, homozygotes display strongly reduced TNF levels in spleen relative to wild-type controls

• in response to stimulation with LPS, lipoteichoic acid (LTA), E. coli, and HKLM, mutant BMDMs display strongly reduced TNF release relative to similarly-treated wild-type BMDMs

increased susceptibility to bacterial infection ( J:76161 )

• at 72 hrs (but not at 48 hrs) post-infection with 1.5 x 10⁵ CFU/kg virulent L. monocytogenes, homozygotes display a strongly increased bacterial load in spleen and lung relative to wild-type controls, with no differences in total blood leukocyte numbers

increased susceptibility to bacterial infection induced morbidity/mortality ( J:76161 )

• in response to i.v. injection with 1.5 x 10⁵ CFU/kg virulent L. monocytogenes, only 1 of 7 homozygotes (vs 9 of 10 wild-type controls) survive the 14-day observation period post-infection

• however, all homozygotes survive L. monocytogenes infection with 10⁴ CFU/kg

hematopoietic system

impaired macrophage phagocytosis ( J:76161 )

• in an optimized quantitative phagocytosis assay, mutant bone marrow-derived macrophages (BMDMs) display reduced uptake of rhodamine-labeled E. coli particles relative to wild-type BMDMs

• however, macrophage generation of NO and oxidative burst activity in response to L. monocytogenes are both normal

cellular

impaired macrophage phagocytosis ( J:76161 )

• in an optimized quantitative phagocytosis assay, mutant bone marrow-derived macrophages (BMDMs) display reduced uptake of rhodamine-labeled E. coli particles relative to wild-type BMDMs

• however, macrophage generation of NO and oxidative burst activity in response to L. monocytogenes are both normal

Genotype
MGI:4367112

cx4

• Allelic Composition: Ldlr^tm1Her/Ldlr^tm1Her; Mapkapk2^tm1Mgl/Mapkapk2^tm1Mgl
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6

cardiovascular system

arteriosclerosis ( J:142788 )

• reduced development of atherosclerosis after 8-16 weeks on an atherogenic diet

hematopoietic system

abnormal macrophage derived foam cell morphology ( J:142788 )

• reduced in number among peritoneal macrophage in mice fed an atherogenic diet for 10 weeks

decreased macrophage cell number ( J:142788 )

• decreased macrophage content in longitudinal sections of the aortic arch

homeostasis/metabolism

increased circulating cholesterol level ( J:142788 )

• increased plasma cholesterol relative to mice deficient only in Ldlr

• increased non-HDL cholesterol relative to mice deficient only in Ldlr

immune system

abnormal macrophage derived foam cell morphology ( J:142788 )

• reduced in number among peritoneal macrophage in mice fed an atherogenic diet for 10 weeks

decreased macrophage cell number ( J:142788 )

• decreased macrophage content in longitudinal sections of the aortic arch

cellular

abnormal macrophage derived foam cell morphology ( J:142788 )

• reduced in number among peritoneal macrophage in mice fed an atherogenic diet for 10 weeks

Genotype
MGI:3698632

cx5

• Allelic Composition: Mapkapk2^tm1Mgl/Mapkapk2^tm1Mgl; Mapkapk3^tm1.1Lex/Mapkapk3^tm1.1Lex
• Genetic Background: involves: 129P2/OlaHsd * 129S/SvEvBrd * C57BL/6

mortality/aging

mortality/aging ( J:117668 )

N • in contrast to expectations, mice are viable

immune system

abnormal cytokine secretion ( J:117668 )

• LPS-induced production of tristetraprolin and TNF is reduced compared to wild-type mice and compared to Mapkapk2 single homozygotes

embryo

embryo phenotype ( J:117668 )

N • in contrast to expectations, no defects in embryonic development are detected

Genotype
MGI:3629603

cx6

• Allelic Composition: Mapkapk2^tm1Mgl/Mapkapk2^tm1Mgl; Tnf^tm2Gkl/Tnf⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S/SvEv * C57BL/6J

mortality/aging

premature death ( J:108572 )

• increase in mortality from 8 weeks of age onward

cellular

decreased apoptosis ( J:108572 )

• mice have fewer apoptotic cells in inflamed ileal tissue compared to Tnf^tm2Gkl/+ controls

immune system

immune system phenotype ( J:108572 )

N • there is no change in CD4+ to CD8+ ratios compared to findings in Tnf^tm2Gkl/+ single mutants

small intestinal inflammation ( J:108572 )

• Tnf^tm2Gkl phenotype is exacerbated in these mice

granulomatous inflammation ( J:108572 )

• IBD is associated with early formation of multiple granulomas

digestive/alimentary system

small intestinal inflammation ( J:108572 )

• Tnf^tm2Gkl phenotype is exacerbated in these mice