Phenotypes Associated with This Genotype

Genotype
MGI:3622062

• Allelic Composition: Tnf^tm1Gkl/Tnf^tm2Gkl
• Genetic Background: involves: 129S/SvEv * C57BL/6

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

immune system

increased circulating tumor necrosis factor level ( J:54056 )

• at 6 weeks of age circulating levels of TNF are up between 90 and 430 pg/ml compared to undetectable levels in wild-type mice

increased tumor necrosis factor secretion ( J:54056 )

• increased basal and LPS-induced secretion of TNF from thioglycollate-elicited peritoneal macrophages and bone marrow-derived macrophages

• spleen derived T lymphocytes have 3-fold greater TNF production and prolonged mRNA accumulation after incubation with an agonistic anti-CD3 antibody

• splenic B220+ cells also show increased basal and mitogen-stimulated TNF production

• primary synovial and lung fibroblasts display spontaneous TNF secretion and increased secretion following LPS stimulation unlike controls

rheumatoid arthritis ( J:54056 )

• disease onset occurs at 6-8 weeks of age

• early signs include hyperplasia of the synovial membrane and the presence of polymorphonuclear infiltrates; progressing to pannus and fibrous tissue formation, subchondral bone erosion, and articular cartilage destruction

• both IgM and IgG are detected in arthritic joints

increased susceptibility to endotoxin shock ( J:54056 )

• increased sensitivity to LPS-induced mortality with 5 of 10 dying after injection of 100 ug/ 25 g compared to complete survival of control mice at the same dose

skeleton

rheumatoid arthritis ( J:54056 )

• disease onset occurs at 6-8 weeks of age

• early signs include hyperplasia of the synovial membrane and the presence of polymorphonuclear infiltrates; progressing to pannus and fibrous tissue formation, subchondral bone erosion, and articular cartilage destruction

• both IgM and IgG are detected in arthritic joints

homeostasis/metabolism

increased circulating tumor necrosis factor level ( J:54056 )

• at 6 weeks of age circulating levels of TNF are up between 90 and 430 pg/ml compared to undetectable levels in wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
inflammatory bowel disease		DOID:0050589	OMIM:PS266600	J:54056
rheumatoid arthritis		DOID:7148	OMIM:180300	J:54056