Mouse Genome Informatics
hm1
    Tnfrsf1atm1Blt/Tnfrsf1atm1Blt
B6.129P2-Tnfrsf1atm1Blt
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 spinal cord compared to wild-type or Tnfrsf1btm1Mwm homozygotes
• 7 days after traumatic spinal cord injury the rostrocaudal spread of the lesion is increased and tissue destruction is more severe compared to wild-type mice
• 4 weeks after traumatic spinal cord injury locomotor performance is significantly more impaired and lesions are longer

behavior/neurological
• after sleep deprivation, mice exhibit increased slow 'slow waves' and negative rebound during the dark period unlike wild-type mice


Mouse Genome Informatics
hm2
    Tnfrsf1atm1Blt/Tnfrsf1atm1Blt
C.129P2-Tnfrsf1atm1Blt
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• decreased mortality is seen after exposure to 750 mg acetaminophen /kg

homeostasis/metabolism
• decreased mortality is seen after exposure to 750 mg acetaminophen /kg
• little or no liver damage, reduced infiltration of neutrophils and macrophages into the liver, and reduced intrahepatic chemokine production are seen after exposure to 600 mg acetaminophen /kg


Mouse Genome Informatics
hm3
    Tnfrsf1atm1Blt/Tnfrsf1atm1Blt
involves: 129/Sv * 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• following exposure to Pseudomonas aerugiosa exotoxin

immune system
• mice exhibit reduced Pseudomonas aerugiosa exotoxin-induced liver failure compared with similarly treated wild-type mice


Mouse Genome Informatics
hm4
    Tnfrsf1atm1Blt/Tnfrsf1atm1Blt
involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• organized follicular dendritic cell networks are absent
• the typical subepithelial dome areas fail to form
• B cells are present but no organized follicles are seen and organized follicular dendritic cell networks are absent
• average of 2 - 4 per mouse compared to 6 - 8 in wild-type mice
• however, T cell populations in the thymus and T and B cell populations in the spleen and lymph nodes are normal
• B cell follicles and follicular dendritic cell network formation are impaired in mesenteric and peripheral lymph nodes; however B cells are present and B and T cell areas are segregated
• following treatment with MOG
• significant reduction in bronchoalveolar lavage leukocytosis in an ovalbumin-induced allergic asthma model
• LPS-induced IL-6 secretion is reduced about 3-fold compared to wild-type mice; however TNF secretion is similar to wild-type
• 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
• infection with as few as 250 colony forming units of Listeria monocytogenes results in 100% mortality by 6 days after infection, all wild-type mice survive this treatment
• D-galactosamine sensitized homozygotes can survive 100-fold higher concentrations of LPS than wild-type; however without D-galactosamine sensitization both types of mice show similar sensitivity to LPS-induced mortality
• however, homozygotes are able to control infections of lymphocytic choriomeningitis virus
• 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
• following treatment with MOG


Mouse Genome Informatics
cn5
    Tg(Cr2-cre)3Cgn/0
Tnfrsf1atm1Blt/Tnfrsf1atm2Gkl

involves: 129P2/OlaHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• architecture of all secondary lymphoid organs is similar to wild-type (J:113314)


Mouse Genome Informatics
cx6
    Tnftm2Gkl/Tnftm2Gkl
Tnfrsf1atm1Blt/Tnfrsf1atm1Blt

involves: 129P2/OlaHsd * 129S/SvEv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• at 6 weeks of age circulating levels of TNF are 320 +/- 160 pg/ml in disease free mutants compared to undetectable levels in wild-type mice
• however, no signs of arthritis or inflammatory bowel disease are detected
• increased basal and LPS-induced secretion of TNF from thioglycollate-elicited peritoneal macrophages and bone marrow-derived macrophages
• primary synovial and lung fibroblasts display spontaneous TNF secretion and increased secretion following LPS stimulation unlike controls

homeostasis/metabolism
• at 6 weeks of age circulating levels of TNF are 320 +/- 160 pg/ml in disease free mutants compared to undetectable levels in wild-type mice
• however, no signs of arthritis or inflammatory bowel disease are detected


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
    Tg(Gfap-TNF*)K21Gkl/0
Tnfrsf1atm1Blt/Tnfrsf1a+

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
nervous system
• neurological symptoms by the sixth month of age, delayed compared to Tg alone
• at 6 months CNS shows symmetrical, focal demyelinated plaques at the capsula interna and in the spinal cord

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