Phenotypes Associated with This Genotype

Genotype
MGI:6272035

• Allelic Composition: Tnf^Bpsm1/Tnf⁺
• Genetic Background: involves: C57BL/6

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

behavior/neurological

decreased grip strength ( J:226052 )

• mice gradually lose grasping strength

hindlimb paralysis ( J:226052 )

• progressive paralysis of the hindlimbs

cardiovascular system

aortic aneurysm ( J:226052 )

• Background Sensitivity: aortic aneurism is much less pronounced on the C57BL/6 background than in mice on a BALB/c background

aortic valve inflammation ( J:226052 )

mitral valve inflammation ( J:226052 )

homeostasis/metabolism

increased circulating tumor necrosis factor level ( J:226052 )

• increase in circulating TNF levels

• however, circulating levels of IL1 beta, IL6, IL18, and IL23 are normal

immune system

aortic valve inflammation ( J:226052 )

mitral valve inflammation ( J:226052 )

increased circulating tumor necrosis factor level ( J:226052 )

• increase in circulating TNF levels

• however, circulating levels of IL1 beta, IL6, IL18, and IL23 are normal

rheumatoid arthritis ( J:226052 )

• mice exhibit a severe symmetrical, erosive chronic polyarthritis that predominately affects the peripheral joints and less severe damage in central joints

• joints show extensive pannus invasion, bone destruction and cartilage erosion

• pannus tissue is mostly F4.80 cells and most affected joints are devoid of lymphocytes and neutrophils

• bone erosion is maximal in joints with the highest load factor

• lethally irradiated wild-type mice transplanted with mutant bone marrow develop arthritis within 5 months

• 5 week old mutant mice transplanted with wild-type bone marrow do not develop arthritis over the following 5 months

• however, mice do not contain IgM or IgG rheumatoid factors and no inflammation is seen in the skin, liver, blood vessels, eyes or gut and no evidence for cartilage or bone repair is seen

limbs/digits/tail

abnormal limb morphology ( J:226052 )

• limbs are deformed and mice gradually show forelimbs that become angled at the wrist level and hind-limb digits become immobile

mortality/aging

mortality/aging ( J:226052 )

N • Background Sensitivity: no mice on the C57BL/6 background die up to 200 days of age while sudden death is seen on the BALB/c background

skeleton

rheumatoid arthritis ( J:226052 )

• mice exhibit a severe symmetrical, erosive chronic polyarthritis that predominately affects the peripheral joints and less severe damage in central joints

• joints show extensive pannus invasion, bone destruction and cartilage erosion

• pannus tissue is mostly F4.80 cells and most affected joints are devoid of lymphocytes and neutrophils

• bone erosion is maximal in joints with the highest load factor

• lethally irradiated wild-type mice transplanted with mutant bone marrow develop arthritis within 5 months

• 5 week old mutant mice transplanted with wild-type bone marrow do not develop arthritis over the following 5 months

• however, mice do not contain IgM or IgG rheumatoid factors and no inflammation is seen in the skin, liver, blood vessels, eyes or gut and no evidence for cartilage or bone repair is seen

abnormal rib joint morphology ( J:226052 )

• the 13th (floating) ribs enter the neural canal instead of being attached to the centrum

abnormal thoracic vertebrae morphology ( J:226052 )

• hunchback is due to erosion of the T10-T13 thoracic vertebrae

abnormal spine curvature ( J:226052 )

• abnormal curvature of the spine at the level of the rib cage

kyphosis ( J:226052 )

• a pronounced hunchback is seen at around 7 months of age associated with the progressive paralysis of hind limbs

joint dislocation ( J:226052 )

• hindpaws of 100 day old mice are luxated at the level of the ankle

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
rheumatoid arthritis		DOID:7148	OMIM:180300	J:226052