Phenotypes Associated with This Genotype

Genotype
MGI:3622060

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

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

mortality/aging

premature death ( J:54056 )

• die between 5 and 12 weeks of age

cardiovascular system

cardiovalvulitis ( J:226052 )

• inflammation of the heart valves

immune system

cardiovalvulitis ( J:226052 )

• inflammation of the heart valves

small intestinal inflammation ( J:54056 )

• first detected between 2 and 4 weeks of age as mucosal abnormalities with intestinal villous blunting and broadening generally confined to the terminal ileum

• becomes severe by 4 weeks, with increased numbers of submucosal lymphoid aggregates and follicles eventually penetrating deep into the muscular layers of the bowel wall

thymus hypoplasia ( J:54056 )

• severe hypoplasia with atrophy and disorganization of the cortical and medullary areas is seen at 4 weeks of age; however at 12 days of age the ratio of thymic and peripheral T cell subsets is normal

increased circulating tumor necrosis factor level ( J:54056 )

• at 6 weeks of age circulating levels of TNF are up to 822 +/- 447 pg/ml compared to undetectable levels in wild-type mice

rheumatoid arthritis ( J:54056 )

• develop signs of chronic polyarthritis including joint swelling, distortion of fore and hind paw morphology, impaired movement

• disease onset occurs at 12 days 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

growth/size/body

decreased body weight ( J:54056 )

• body weight does no exceed 6-7 g

digestive/alimentary system

small intestinal inflammation ( J:54056 )

• first detected between 2 and 4 weeks of age as mucosal abnormalities with intestinal villous blunting and broadening generally confined to the terminal ileum

• becomes severe by 4 weeks, with increased numbers of submucosal lymphoid aggregates and follicles eventually penetrating deep into the muscular layers of the bowel wall

skeleton

rheumatoid arthritis ( J:54056 )

• develop signs of chronic polyarthritis including joint swelling, distortion of fore and hind paw morphology, impaired movement

• disease onset occurs at 12 days 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

hematopoietic system

thymus hypoplasia ( J:54056 )

• severe hypoplasia with atrophy and disorganization of the cortical and medullary areas is seen at 4 weeks of age; however at 12 days of age the ratio of thymic and peripheral T cell subsets is normal

homeostasis/metabolism

increased circulating tumor necrosis factor level ( J:54056 )

• at 6 weeks of age circulating levels of TNF are up to 822 +/- 447 pg/ml compared to undetectable levels in wild-type mice

endocrine/exocrine glands

thymus hypoplasia ( J:54056 )

• severe hypoplasia with atrophy and disorganization of the cortical and medullary areas is seen at 4 weeks of age; however at 12 days of age the ratio of thymic and peripheral T cell subsets is normal

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