Phenotypes associated with this allele

• Allele Symbol: Tnf^tm1Sek
• Allele Name: targeted mutation 1, Kenji Sekikawa
• Allele ID: MGI:2653694
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tnf^tm1Sek/Tnf^tm1Sek	B6.Cg-Tnf^tm1Sek	MGI:3640396
hm2	Tnf^tm1Sek/Tnf^tm1Sek	involves: C57BL/6 * CBA	MGI:2653695
cn3	Stat3^tm2Aki/Stat3^tm2Aki Tnf^tm1Sek/Tnf^tm1Sek Lyz2^tm1(cre)Ifo/Lyz2^+	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:3771397
cx4	Tbk1^tm1Aki/Tbk1^tm1Aki Tnf^tm1Sek/Tnf^tm1Sek	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:3776849
cx5	Nfkbiz^tm1Aki/Nfkbiz^tm1Aki Tnf^tm1Sek/Tnf^tm1Sek	involves: 129P2/OlaHsd * C57BL/6NCrlj * CBA/JNCrlj	MGI:5501495
cx6	Rigi^tm1Aki/Rigi^tm1Aki Tnf^tm1Sek/Tnf^tm1Sek	involves: C57BL/6 * CBA	MGI:3590134

Genotype
MGI:3640396

hm1

• Allelic Composition: Tnf^tm1Sek/Tnf^tm1Sek
• Genetic Background: B6.Cg-Tnf^tm1Sek

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

immune system

immune system phenotype ( J:44841 )

N • mutant mice are viable, fertile and remain healthy up to 60 weeks of age with no signs of acute or chronic infection

N • the number and distribution of thymocytes and splenic T cell populations is normal relative to wild-type controls

absent spleen germinal center ( J:44841 )

• unlike wild-type mice, mutants fail to form spleen germinal centers after i.p. immunization with sheep red blood cells (SRBCs)

abnormal macrophage physiology ( J:44841 )

• after a 16-hr treatment with LPS (1 ug), mutant thioglycollate-elicited peritoneal macrophages show a significant decrease in IL-1alpha, IL-1beta, and IL-6 levels relative to wild-type macrophages

decreased circulating interferon-gamma level ( J:44841 )

• after challenge with a high dose of LPS (800 ug/mouse)

decreased circulating interleukin-1 alpha level ( J:44841 )

• after challenge with a high dose of LPS (800 ug/mouse)

decreased circulating interleukin-1 beta level ( J:44841 )

• after challenge with a high dose of LPS (800 ug/mouse)

decreased circulating interleukin-6 level ( J:44841 )

• after challenge with a high dose of LPS (800 ug/mouse)

abnormal Peyer's patch germinal center morphology ( J:44841 )

• unlike wild-type mice, mutants fail to form germinal centers in Peyer's patches after i.p. immunization with SRBCs

abnormal mesenteric lymph node morphology ( J:44841 )

• unlike wild-type mice, mutants fail to form germinal centers in mesenteric lymph nodes after i.p. immunization with SRBCs

absent lymph node germinal center ( J:44841 )

• at 6-8 weeks of age, mutants fail to form germinal centers in peripheral lymphoid organs after i.p. immunization with SRBCs

abnormal cytokine secretion ( J:44841 )

• after challenge with a high dose of LPS (800 ug/mouse), serum levels of IL-1alpha, IL-1beta, IL-6, and IFN-gamma are significantly reduced by 30% to 60% relative to those in similarly treated wild-type mice

decreased susceptibility to endotoxin shock ( J:44841 )

• whereas all wild-type mice die within 6-9 hrs after injection of 1 ug LPS and 20 mg D-galactosamin (GalN), mutant mice are resistant to endotoxic shock even at 100 ug LPS and 20 mg GalN per mouse

• mutant mice show a lower mortality rate (2 of 5) than wild-type mice (4 of 5) after a high dose injection of LPS (1200 ug/mouse) in the absence of GalN

• unlike wild-type, mutant mice do not exhibit hepatocyte apoptosis or acute hepatitis after a 4-hr treatment with LPS (10 ug/mouse) and GalN (20 mg/mouse)

• however, no differences in thymocyte apoptosis are observed in cortex after a 4-hr treatemnt with LPS (10 ug/mouse) and GalN (20 mg/mouse) or after a 12-hr treatment with a high dose of LPS alone (800 ug/mouse)

hematopoietic system

absent spleen germinal center ( J:44841 )

• unlike wild-type mice, mutants fail to form spleen germinal centers after i.p. immunization with sheep red blood cells (SRBCs)

abnormal macrophage physiology ( J:44841 )

• after a 16-hr treatment with LPS (1 ug), mutant thioglycollate-elicited peritoneal macrophages show a significant decrease in IL-1alpha, IL-1beta, and IL-6 levels relative to wild-type macrophages

behavior/neurological

decreased coping response ( J:102967 )

increased anxiety-related response ( J:102967 )

• mutant mice spend significantly less time in the open arms relative to wild-type mice; this is ameliorated by diazepam treatment

increased grooming behavior ( J:102967 )

• mutant mice show more frequent, longer grooming episodes than wild-type mice

decreased vertical activity ( J:102967 )

• mutant mice show less rearing episodes than wild-type mice in a novel environment

decreased locomotor activity ( J:102967 )

• mutant mice show reduced horizontal activity relative to wild-type mice in the open field test

homeostasis/metabolism

decreased circulating interferon-gamma level ( J:44841 )

• after challenge with a high dose of LPS (800 ug/mouse)

decreased circulating interleukin-1 alpha level ( J:44841 )

• after challenge with a high dose of LPS (800 ug/mouse)

decreased circulating interleukin-1 beta level ( J:44841 )

• after challenge with a high dose of LPS (800 ug/mouse)

decreased circulating interleukin-6 level ( J:44841 )

• after challenge with a high dose of LPS (800 ug/mouse)

increased serotonin level ( J:102967 )

• mutants show an increased level of 5-HT in the hippocampus, medulla oblongata/pons and cerebellum relative to wild-type mice

• increased levels of 5-HIAA are observed in brain

Genotype
MGI:2653695

hm2

• Allelic Composition: Tnf^tm1Sek/Tnf^tm1Sek
• Genetic Background: involves: C57BL/6 * CBA

reproductive system

abnormal vagina weight ( J:114219 )

♀ • at 2 days after estrogen deprivation induced by gonadectomy, mutant females fail to show a decrease in vaginal organ weight, indicating no Fas-mediated vaginal cell death

abnormal female reproductive system physiology ( J:59892 )

♀ • alpha-galactosylceramide induced abortion does not occur

prolonged estrus ( J:114219 )

♀ • vaginal smears indicate a persistent estrous stage

liver/biliary system

abnormal liver physiology ( J:120559 )

• when mice are recipients of wild-type hepatitis B surface antigen (HBsAg)-specific Th1 cells after treatment with HBsAg, severe liver injury is induced

Genotype
MGI:3771397

cn3

• Allelic Composition: Stat3^tm2Aki/Stat3^tm2Aki; Tnf^tm1Sek/Tnf^tm1Sek; Lyz2^tm1(cre)Ifo/Lyz2⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

immune system

colitis ( J:83280 )

• mice develop enterocolitis that is as severe as in Stat3 null mice

increased interferon-gamma secretion ( J:83280 )

• CD4+ cells produce increased levels of interferon-gamma

increased interleukin-12b secretion ( J:83280 )

• macrophages produce increased amounts of IL-12p40 that are comparable to in Stat3 null mice

increased interleukin-6 secretion ( J:83280 )

• macrophages produce increased amounts of IL-6 that are comparable to in Stat3 null mice

digestive/alimentary system

colitis ( J:83280 )

• mice develop enterocolitis that is as severe as in Stat3 null mice

Genotype
MGI:3776849

cx4

• Allelic Composition: Tbk1^tm1Aki/Tbk1^tm1Aki; Tnf^tm1Sek/Tnf^tm1Sek
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

mortality/aging

mortality/aging ( J:132662 )

N • the Tnf null background prevents the lethality that occurs at E14.5 for Tbk1 homozygotes

immune system

decreased IgG level ( J:132662 )

• serum titers of antigen specific IgG in response to a DNA vaccine are almost 4-log lower than those in control

• when mice serve as bone marrow donors to irradiated control mice, similar defects in antigen specific IgG production after immunization are observed

decreased IgG1 level ( J:132662 )

• serum titers of antigen specific IgG1 in response to a DNA vaccine are significantly less

decreased IgG2a level ( J:132662 )

• serum titers of antigen specific IgG2a in response to a DNA vaccine are significantly les

• when mice serve as bone marrow donors to irradiated control mice, similar defects in antigen specific IgG2a production after immunization are observed

abnormal cytotoxic T cell physiology ( J:132662 )

• there is a 10-fold reduction in the number of antigen specific CD8 T cells two weeks after immunization with a DNA vaccine compared to vaccinated controls

• when mice are irradiated and receive wild-type bone marrow, CD8 T cells proliferate at a significantly reduced level upon exposure to antigen encoded in the DNA vaccine

decreased cytotoxic T cell cytolysis ( J:132662 )

• there is a reduction in antigen specific CTL activity two weeks after immunization with a DNA vaccine compared to vaccinated controls

decreased interferon-gamma secretion ( J:132662 )

• splenocytes from mice immunized with a DNA vaccine produce significantly less IFN-gamma upon stimulation with antigen in culture compared to vaccinated controls

• when mice serve as bone marrow donors to irradiated control mice, similar defects in IFN-gamma secretion after immunization are observed

hematopoietic system

decreased IgG level ( J:132662 )

• serum titers of antigen specific IgG in response to a DNA vaccine are almost 4-log lower than those in control

• when mice serve as bone marrow donors to irradiated control mice, similar defects in antigen specific IgG production after immunization are observed

decreased IgG1 level ( J:132662 )

• serum titers of antigen specific IgG1 in response to a DNA vaccine are significantly less

decreased IgG2a level ( J:132662 )

• serum titers of antigen specific IgG2a in response to a DNA vaccine are significantly les

• when mice serve as bone marrow donors to irradiated control mice, similar defects in antigen specific IgG2a production after immunization are observed

abnormal cytotoxic T cell physiology ( J:132662 )

• there is a 10-fold reduction in the number of antigen specific CD8 T cells two weeks after immunization with a DNA vaccine compared to vaccinated controls

• when mice are irradiated and receive wild-type bone marrow, CD8 T cells proliferate at a significantly reduced level upon exposure to antigen encoded in the DNA vaccine

decreased cytotoxic T cell cytolysis ( J:132662 )

• there is a reduction in antigen specific CTL activity two weeks after immunization with a DNA vaccine compared to vaccinated controls

Genotype
MGI:5501495

cx5

• Allelic Composition: Nfkbiz^tm1Aki/Nfkbiz^tm1Aki; Tnf^tm1Sek/Tnf^tm1Sek
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6NCrlj * CBA/JNCrlj

vision/eye

eyelid edema ( J:194832 )

conjunctivitis ( J:194832 )

• infiltration of B cells into the conjunctiva

immune system

conjunctivitis ( J:194832 )

• infiltration of B cells into the conjunctiva

dermatitis ( J:194832 )

• heavy infiltration of lymphocytes into dermis

• infiltrating T cells are mostly CD4+

integument

dermatitis ( J:194832 )

• heavy infiltration of lymphocytes into dermis

• infiltrating T cells are mostly CD4+

homeostasis/metabolism

eyelid edema ( J:194832 )

craniofacial

eyelid edema ( J:194832 )

growth/size/body

eyelid edema ( J:194832 )

Genotype
MGI:3590134

cx6

• Allelic Composition: Rigi^tm1Aki/Rigi^tm1Aki; Tnf^tm1Sek/Tnf^tm1Sek
• Genetic Background: involves: C57BL/6 * CBA

mortality/aging

postnatal lethality ( J:100539 )

• only 1 double homozygous viable pup out of 43 pups born from intercrossing Ddx58^tm1Aki heterozygous and Tnf^tm1Sek homozygous mice

• specific time of death was not reported

• lethality is similar to Ddx58^tm1Aki heterozygous mice and no rescue was observed