Mouse Genome Informatics
hm1
    Tnftm3Gkl/Tnftm3Gkl
involves: 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
• primary B cell follicles are absent and a ring-like B cell area typical of TNF-deficient mice is present
• after immunization with sheep red blood cells (SRBCs), mutants fail to form organized germinal centers
• after intraperitoneal injection of SRBC, mutants exhibit severely impaired SRBC-specific IgG1 antibody responses
• levels of IgG1 specific for SRBC are lower than in wild-type
• mutant mice exhibit physiologically relevant levels of biologically active transmembrane TNF protein in the complete absence of biologically active soluble TNF
• mesenteric lymph nodes (MLN) and spleen of mutants lack follicular dendritic cells
• mesenteric lymph nodes (MLN) lack organized B cell follicles but occasionally have GC-like regions that are centered in B cell areas
• mesenteric lymph nodes lack organized B cell follicles and follicular dendritic cell networks
• mutant mice exhibit physiologically relevant levels of biologically active transmembrane TNF protein in the complete absence of biologically active soluble TNF
• mutant spleen cells isolated 49 days after myelin oligondendrocyte glycoprotein (MOG) showed no memory
• failed to proliferate in response to MOG peptide treatment
• 25 days after injection with pertussis toxin, it is observed that experimental allergic encephalomyelitis (EAE) is completely suppressed compared to wild-type
• when treated with D-gal (a hepatotoxin) at 20 mg/animal and doses of lipopolysaccharide (LPS) up to 100ug/25g body weight, mutants are completely resistant to LPS-induced death, but wild-type mice all die at 100-fold lower LPS doses
• with challenge at high doses (10000 cfu) of Listeria monocytogenes (LM), mutants show high sensitivity with maximal lethality at 6 days post-infection, compared to wild-type; mutants show significant resistance when challenged with a physiological dose of LM (100 cfu)

hematopoietic system
• primary B cell follicles are absent and a ring-like B cell area typical of TNF-deficient mice is present
• after immunization with sheep red blood cells (SRBCs), mutants fail to form organized germinal centers
• after intraperitoneal injection of SRBC, mutants exhibit severely impaired SRBC-specific IgG1 antibody responses
• levels of IgG1 specific for SRBC are lower than in wild-type

homeostasis/metabolism
• mutant mice exhibit physiologically relevant levels of biologically active transmembrane TNF protein in the complete absence of biologically active soluble TNF


Mouse Genome Informatics
cx2
    Tnftm3Gkl/Tnftm3Gkl
Zfp36tm1Pjb/Zfp36tm1Pjb

involves: 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
N
• up to 7 months of age, double mutants appear phenotypically normal and lack joint inflammation, cartilage erosion, and pannus formation compared to TNF-sufficient, Zpf36-null littermates which develop joint swelling and cachexia by 7 months (J:114740)
• double mutants exhibit myeloid hyperplasia, similar to TNF-sufficient, Zpf36-null littermates

hematopoietic system
• double mutants exhibit myeloid hyperplasia, similar to TNF-sufficient, Zpf36-null littermates