Phenotypes Associated with This Genotype

Genotype
MGI:3053718

• Allelic Composition: Tg(TNF)197Gkl/0
• Genetic Background: involves: C57BL/6 * CBA

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

growth/size/body

decreased body weight ( J:97992 )

• reduction of >20% in body weight

weight loss ( J:92576 )

• progressive weight loss is seen as a result of progressive arthritis

immune system

abnormal osteoclast differentiation ( J:97992 )

• increased osteoclast numbers after subperiosteal injection of LPS into the calvarial bone compared with wild-type mice

• enhanced in vitro osteoclast formation stimulated with TNF in cells derived from mutant mice compared with wild-type mice

• enhanced in vitro osteoclastogenesis in spleen cells in the presence of M-CSF and receptor activator of NF-kappaB ligand (RANKL)

• higher proliferative activity in osteoclasts in spleen cells in the presence of M-CSF and RANKL

increased osteoclast cell number ( J:97992 )

• increased osteoclast numbers after subperiosteal injection of LPS into the calvarial bone compared with wild-type mice

arthritis ( J:92576 , J:97992 )

• at 3-4 weeks of age swelling of the ankle joints is evident followed by progressive impairment of hind leg movement resulting in the inability to move the hind legs by 9-10 weeks of age (J:92576)

• hyperplasia of the synovial membrane along with inflammatory infiltrates, articular cartilage destruction, and fibrosis are all seen in the joints (J:92576)

• arthritis at the age of 4 week (J:97992)

behavior/neurological

decreased grip strength ( J:97992 )

• loss of grip strength of paws

skeleton

abnormal osteoclast differentiation ( J:97992 )

• increased osteoclast numbers after subperiosteal injection of LPS into the calvarial bone compared with wild-type mice

• enhanced in vitro osteoclast formation stimulated with TNF in cells derived from mutant mice compared with wild-type mice

• enhanced in vitro osteoclastogenesis in spleen cells in the presence of M-CSF and receptor activator of NF-kappaB ligand (RANKL)

• higher proliferative activity in osteoclasts in spleen cells in the presence of M-CSF and RANKL

increased osteoclast cell number ( J:97992 )

• increased osteoclast numbers after subperiosteal injection of LPS into the calvarial bone compared with wild-type mice

joint swelling ( J:97992 )

• progressive joint swelling

arthritis ( J:92576 , J:97992 )

• at 3-4 weeks of age swelling of the ankle joints is evident followed by progressive impairment of hind leg movement resulting in the inability to move the hind legs by 9-10 weeks of age (J:92576)

• hyperplasia of the synovial membrane along with inflammatory infiltrates, articular cartilage destruction, and fibrosis are all seen in the joints (J:92576)

• arthritis at the age of 4 week (J:97992)

decreased trabecular bone volume ( J:97992 )

• lower trabecular bone volume

decreased bone mass ( J:97992 )

• bone loss in both the axial and peripheral skeletal compartment

increased bone resorption ( J:97992 )

• extensive areas of bone resorption in spleen cells in the presence of M-CSF and RANKL

• bigger and higher number of osteoclasts and increased capacity to form resorption pits

• osteoclasts form earlier, more abundantly, and persisted for a longer time

hematopoietic system

abnormal osteoclast differentiation ( J:97992 )

• increased osteoclast numbers after subperiosteal injection of LPS into the calvarial bone compared with wild-type mice

• enhanced in vitro osteoclast formation stimulated with TNF in cells derived from mutant mice compared with wild-type mice

• enhanced in vitro osteoclastogenesis in spleen cells in the presence of M-CSF and receptor activator of NF-kappaB ligand (RANKL)

• higher proliferative activity in osteoclasts in spleen cells in the presence of M-CSF and RANKL

increased osteoclast cell number ( J:97992 )

• increased osteoclast numbers after subperiosteal injection of LPS into the calvarial bone compared with wild-type mice

cellular

abnormal osteoclast differentiation ( J:97992 )

• increased osteoclast numbers after subperiosteal injection of LPS into the calvarial bone compared with wild-type mice

• enhanced in vitro osteoclast formation stimulated with TNF in cells derived from mutant mice compared with wild-type mice

• enhanced in vitro osteoclastogenesis in spleen cells in the presence of M-CSF and receptor activator of NF-kappaB ligand (RANKL)

• higher proliferative activity in osteoclasts in spleen cells in the presence of M-CSF and RANKL

homeostasis/metabolism

joint swelling ( J:97992 )

• progressive joint swelling

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
rheumatoid arthritis		DOID:7148	OMIM:180300	J:92576