Mouse Genome Informatics
hm1
    Tnftm1Sek/Tnftm1Sek
B6.Cg-Tnftm1Sek
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• mutant mice are viable, fertile and remain healthy up to 60 weeks of age with no signs of acute or chronic infection (J:44841)
• the number and distribution of thymocytes and splenic T cell populations is normal relative to wild-type controls (J:44841)
• unlike wild-type mice, mutants fail to form spleen germinal centers after i.p. immunization with sheep red blood cells (SRBCs)
• 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
• after challenge with a high dose of LPS (800 ug/mouse)
• after challenge with a high dose of LPS (800 ug/mouse)
• after challenge with a high dose of LPS (800 ug/mouse)
• after challenge with a high dose of LPS (800 ug/mouse)
• unlike wild-type mice, mutants fail to form germinal centers in Peyer's patches after i.p. immunization with SRBCs
• unlike wild-type mice, mutants fail to form germinal centers in mesenteric lymph nodes after i.p. immunization with SRBCs
• at 6-8 weeks of age, mutants fail to form germinal centers in peripheral lymphoid organs after i.p. immunization with SRBCs
• 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
• 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
• unlike wild-type mice, mutants fail to form spleen germinal centers after i.p. immunization with sheep red blood cells (SRBCs)
• 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
• mutant mice spend significantly less time in the open arms relative to wild-type mice; this is ameliorated by diazepam treatment
• mutant mice show more frequent, longer grooming episodes than wild-type mice
• mutant mice show less rearing episodes than wild-type mice in a novel environment
• mutant mice show reduced horizontal activity relative to wild-type mice in the open field test

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


Mouse Genome Informatics
hm2
    Tnftm1Sek/Tnftm1Sek
involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
• 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 (J:114219)
• alpha-galactosylceramide induced abortion does not occur (J:59892)
• vaginal smears indicate a persistent estrous stage (J:114219)

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


Mouse Genome Informatics
cn3
    Stat3tm2Aki/Stat3tm2Aki
Tnftm1Sek/Tnftm1Sek
Lyz2tm1(cre)Ifo/Lyz2+

involves: 129P2/OlaHsd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• mice develop enterocolitis that is as severe as in Stat3 null mice
• CD4+ cells produce increased levels of interferon-gamma
• macrophages produce increased amounts of IL-12p40 that are comparable to in Stat3 null mice
• macrophages produce increased amounts of IL-6 that are comparable to in Stat3 null mice

digestive/alimentary system
• mice develop enterocolitis that is as severe as in Stat3 null mice


Mouse Genome Informatics
cx4
    Tbk1tm1Aki/Tbk1tm1Aki
Tnftm1Sek/Tnftm1Sek

involves: 129P2/OlaHsd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• the Tnf null background prevents the lethality that occurs at E14.5 for Tbk1 homozygotes (J:132662)

immune system
• 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
• serum titers of antigen specific IgG1 in response to a DNA vaccine are significantly less
• 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
• 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
• there is a reduction in antigen specific CTL activity two weeks after immunization with a DNA vaccine compared to vaccinated controls
• 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
• 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
• serum titers of antigen specific IgG1 in response to a DNA vaccine are significantly less
• 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
• 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
• there is a reduction in antigen specific CTL activity two weeks after immunization with a DNA vaccine compared to vaccinated controls


Mouse Genome Informatics
cx5
    Nfkbiztm1Aki/Nfkbiztm1Aki
Tnftm1Sek/Tnftm1Sek

involves: 129P2/OlaHsd * C57BL/6NCrlj * CBA/JNCrlj
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
vision/eye
• infiltration of B cells into the conjunctiva

immune system
• infiltration of B cells into the conjunctiva
• heavy infiltration of lymphocytes into dermis
• infiltrating T cells are mostly CD4+

integument
• heavy infiltration of lymphocytes into dermis
• infiltrating T cells are mostly CD4+

homeostasis/metabolism


Mouse Genome Informatics
cx6
    Ddx58tm1Aki/Ddx58tm1Aki
Tnftm1Sek/Tnftm1Sek

involves: C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• only 1 double homozygous viable pup out of 43 pups born from intercrossing Ddx58 heterozygous and Tnf homozygous mice
• specific time of death was not reported
• lethality is similar to Ddx58 heterozygous mice and no rescue was observed