Mouse Genome Informatics
hm1
    Tnfrsf1btm1Mwm/Tnfrsf1btm1Mwm
B6.129S2-Tnfrsf1btm1Mwm
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• 7 days after traumatic spinal cord injury increased cell death is seen in the center of the lesion and the rostrocaudal spread of the lesion is increased compared to wild-type
• 4 weeks after traumatic spinal cord injury locomotor performance is significantly more impaired but lesions are not significantly longer than in wild-type mice

behavior/neurological
• mice exhibit reduced rapid eye movement (REM) sleep episode frequency compared with wild-type mice
• after sleep deprivation, mice exhibit a greater increase in fast 'slow waves' compared with wild-type mice
• however, a decrease in non-REM sleep episode frequency is compensated by extension of non-REM sleep episode duration


Mouse Genome Informatics
hm2
    Tnfrsf1btm1Mwm/Tnfrsf1btm1Mwm
B6.129S2-Tnfrsf1btm1Mwm/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• proliferation of lymph node T cells is reduced in response to anti-CD3e monoclonal antibody stimulation as compared to wild-type
• purified CD8+ T cells require a 5 fold greater anti-CD3 stimulation for tritiated thymidine incorporation equivalent to wild-type, however proliferation is increased in the presence of IL2
• purified CD4+ T cells require a greater anti-CD3 stimulation for tritiated thymidine incorporation, however proliferation is increased in the presence of IL2
• CD8+ T cells produce less interferon gamma following anti-CD3 stimulation than control cells; the result of fewer cells expressing interferon gamma as well as a decrease in the amount produced per cell
• CD8+ T cells exhibit a reduction in IL2 secretion following anti-CD3 stimulation

hematopoietic system
• proliferation of lymph node T cells is reduced in response to anti-CD3e monoclonal antibody stimulation as compared to wild-type
• purified CD8+ T cells require a 5 fold greater anti-CD3 stimulation for tritiated thymidine incorporation equivalent to wild-type, however proliferation is increased in the presence of IL2
• purified CD4+ T cells require a greater anti-CD3 stimulation for tritiated thymidine incorporation, however proliferation is increased in the presence of IL2


Mouse Genome Informatics
hm3
    Tnfrsf1btm1Mwm/Tnfrsf1btm1Mwm
involves: 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• mice exhibit reduced Pseudomonas aerugiosa exotoxin-induced liver failure compared with similarly treated wild-type mice
• T. gondii-exposed mice exhibit increased bacterial load compared with similarly treated wild-type mice
• however, recruitment and intracerebral cell movement is normal in T. gondii-exposed mice


Mouse Genome Informatics
hm4
    Tnfrsf1btm1Mwm/Tnfrsf1btm1Mwm
involves: 129S2/SvPas * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• decreased sensitivity to exogenous tumor necrosis factor (TNF), however, death occurs at high doses
• increased mortality as compared to wild-type following injection with Listeria monocytogenes


Mouse Genome Informatics
hm5
    Tnfrsf1btm1Mwm/Tnfrsf1btm1Mwm
involves: 129S2/SvPas * C57BL/6J * NOD
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• at 5 weeks, mice exhibit periinsulits, while transgenic littermates show severe insulitis
• none of the animals develop diabetes until 24 weeks (no blood glucose measure of >300 mg/dl)

endocrine/exocrine glands
• at 5 weeks, mice exhibit periinsulits, while transgenic littermates show severe insulitis


Mouse Genome Informatics
cx6
    Tnfrsf1atm1Gkl/Tnfrsf1atm1Gkl
Tnfrsf1btm1Mwm/Tnfrsf1btm1Mwm

involves: 129/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• liver inflammation is seen by 3-4 weeks of age and persists throughout adulthood
• no change in the severity of liver inflammation is seen

liver/biliary system
• liver inflammation is seen by 3-4 weeks of age and persists throughout adulthood
• no change in the severity of liver inflammation is seen


Mouse Genome Informatics
cx7
    Ifngtm1Ts/Ifngtm1Ts
Tnfrsf1atm1Blt/Tnfrsf1atm1Blt
Tnfrsf1btm1Mwm/Tnfrsf1btm1Mwm

involves: 129P2/OlaHsd * 129S2/SvPas * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• in pulmonary lavage fluid 4 weeks after infection with Pneumocystis carinii relative to infected controls
• in pulmonary lavage fluid 4 weeks after infection with Pneumocystis carinii relative to infected controls
• in pulmonary lavage fluid 4 weeks after infection with Pneumocystis carinii relative to infected controls
• despite the absence of germinal centers the white pulp has distinct T and B cell areas
• grossly unidentifiable and histologically hypoplastic
• thin and lack primary and secondary cortical follicles
• develop severe inflammation 4 weeks after infection with Pneumocystis carinii
• 4 weeks after infection with Pneumocystis carinii lungs demonstrate severe infection indicating mice are unable to clear the infection
• 4 weeks after infection with Pneumocystis carinii pulmonary lavages contain about 10 fold higher numbers of leukocytes compared to similarly infected control mice

hematopoietic system
• in pulmonary lavage fluid 4 weeks after infection with Pneumocystis carinii relative to infected controls
• in pulmonary lavage fluid 4 weeks after infection with Pneumocystis carinii relative to infected controls
• in pulmonary lavage fluid 4 weeks after infection with Pneumocystis carinii relative to infected controls
• despite the absence of germinal centers the white pulp has distinct T and B cell areas

respiratory system
• develop severe inflammation 4 weeks after infection with Pneumocystis carinii


Mouse Genome Informatics
cx8
    Tnfrsf1atm1Blt/Tnfrsf1atm1Blt
Tnfrsf1btm1Mwm/Tnfrsf1btm1Mwm

involves: 129P2/OlaHsd * 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• mice are able to clear infections of Pneumocystis carinii similar to controls (J:119206)
• despite the absence of germinal centers the white pulp has distinct T and B cell areas
• following treatment with MOG
• grossly unidentifiable and histologically hypoplastic
• thin and lack primary and secondary cortical follicles
• following treatment with MOG, mice exhibit delayed onset, decreased severity of disease, a 6-fold reduction in demyelination area, and decreased MOG-specific IgG response but increased number of inflammatory foci compared with similarly treated wild-type mice
• T. gondii-exposed mice exhibit increased bacterial load compared with similarly treated wild-type mice
• however, recruitment and intracerebral cell movement is normal in T. gondii-exposed mice

hematopoietic system
• despite the absence of germinal centers the white pulp has distinct T and B cell areas
• following treatment with MOG


Mouse Genome Informatics
cx9
    Tnftm2Gkl/Tnf+
Tnfrsf1btm1Mwm/Tnfrsf1btm1Mwm

involves: 129S/SvEv * 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• at 1-5 months of age, only mild intestinal inflammation and no signs of transmural inflammation are seen, unlike in mice heterozygous for Tnftm2Gkl only
• arthritis is more aggressive and destructive than in mice heterozygous for Tnftm2Gkl only with increased swelling of the joints, synovial hyperplasia, numbers of polymorphonuclear infiltrates, and destruction of bone and cartilage

digestive/alimentary system
• at 1-5 months of age, only mild intestinal inflammation and no signs of transmural inflammation are seen, unlike in mice heterozygous for Tnftm2Gkl only

skeleton
• arthritis is more aggressive and destructive than in mice heterozygous for Tnftm2Gkl only with increased swelling of the joints, synovial hyperplasia, numbers of polymorphonuclear infiltrates, and destruction of bone and cartilage


Mouse Genome Informatics
cx10
    Tg(Tnf)6074Gkl/0
Tnfrsf1btm1Mwm/Tnfrsf1btm1Mwm

involves: 129S2/SvPas * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• in 4 week old mice
• in 4 week old mice
• cerebellum myelin vacuolation in 4 week old mice

immune system
• in 4 week old mice

cellular
• in 4 week old mice

Mouse Models of Human Disease
OMIM IDRef(s)
Multiple Sclerosis, Susceptibility To; MS 126200 J:106592


Mouse Genome Informatics
cx11
    Krt8tm1Rgo/Krt8tm1Rgo
Tnfrsf1btm1Mwm/Tnfrsf1btm1Mwm

involves: 129S2/SvPas * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• survival improved 4 fold in the absence of maternal TNFRSF1b as compared to the condition in which TNFRSF1b was present
• survival continues to be reduced


Mouse Genome Informatics
cx12
    Tg(INS-Il10)#Sar/0
Tnfrsf1btm1Mwm/Tnfrsf1btm1Mwm

involves: 129S2/SvPas * C57BL/6J * NOD
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• 100% of deficient transgenic animals develop diabetes by 5 weeks (blood glucose >300 mg/dl), while only 60% of non-transgenic littermates develop diabetes by 24 weeks

homeostasis/metabolism
• mice are considered diabetic after a blood glucose measure of >300 mg/dl