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Phenotypes Associated with This Genotype
Genotype
MGI:3053718
Allelic
Composition
Tg(TNF)197Gkl/0
Genetic
Background
involves: C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(TNF)197Gkl mutation (2 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• reduction of >20% in body weight
• progressive weight loss is seen as a result of progressive arthritis

immune system
• 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 numbers after subperiosteal injection of LPS into the calvarial bone compared with wild-type mice
• 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
• loss of grip strength of paws

skeleton
• 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 numbers after subperiosteal injection of LPS into the calvarial bone compared with wild-type mice
• 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)
• lower trabecular bone volume
• bone loss in both the axial and peripheral skeletal compartment
• progressive joint swelling
• 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
• 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 numbers after subperiosteal injection of LPS into the calvarial bone compared with wild-type mice

cellular
• 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

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


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
10/15/2019
MGI 6.14
The Jackson Laboratory