Phenotypes associated with this allele

• Allele Symbol: Tg(TNF)197Gkl
• Allele Name: transgene insertion 197, George Kollias
• Allele ID: MGI:3053711
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Tg(TNF)197Gkl/0 Tnfrsf1a^tm1.1Gkl/Tnfrsf1a^tm1.1Gkl	involves: 129 * C57BL/6 * CBA	MGI:3053722
cx2	Cd44^tm1Hbg/Cd44^tm1Hbg Tg(TNF)197Gkl/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA	MGI:4941053
tg3	Tg(TNF)197Gkl/0	involves: C57BL/6 * CBA	MGI:3053718

Genotype
MGI:3053722

cx1

• Allelic Composition: Tg(TNF)197Gkl/0; Tnfrsf1a^tm1.1Gkl/Tnfrsf1a^tm1.1Gkl
• Genetic Background: involves: 129 * C57BL/6 * CBA

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

immune system

arthritis ( J:92470 )

• accelerated development of arthritis is seen with earlier and more severe pannus formation, articular cartilage destruction, and bone erosion

skeleton

arthritis ( J:92470 )

• accelerated development of arthritis is seen with earlier and more severe pannus formation, articular cartilage destruction, and bone erosion

Genotype
MGI:4941053

cx2

• Allelic Composition: Cd44^tm1Hbg/Cd44^tm1Hbg; Tg(TNF)197Gkl/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA

growth/size/body

decreased body weight ( J:97992 )

• reduction of >20% in body weight

skeleton

abnormal osteoclast morphology ( J:97992 )

• increased size of osteoclasts compared with Tg(HBB-TNF)197Gkl mice

abnormal osteoclast differentiation ( J:97992 )

• more enhanced in vitro osteoclastogenesis in spleen cells in the presence of M-CSF and receptor activator of NF-kappaB ligand than cells in Tg(HBB-TNF)197Gkl mice

• extensive areas of bone resorption

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

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

• higher proliferative activity in osteoclasts

• reduced rate of apoptosis in osteoclasts

increased osteoclast cell number ( J:97992 )

• increased numbers of osteoclasts compared with Tg(HBB-TNF)197Gkl mice

joint swelling ( J:97992 )

• progressive joint swelling

arthritis ( J:97992 )

• arthritis at the age of 4 week

• disease activity is significantly enhanced and progress significantly faster compared with Tg(HBB-TNF)197Gkl mice

• larger areas of inflammatory bone erosions

decreased trabecular bone volume ( J:97992 )

• lower trabecular bone volume, further decreased than Tg(HBB-TNF)197Gkl mice

• low numbers of trabeculae and decreased trabecular thickness

decreased compact bone thickness ( J:97992 )

• thinning of cortical bone

decreased bone mass ( J:97992 )

• aggravated bone loss in both the axial and peripheral skeletal compartment

decreased trabecular bone mass ( J:97992 )

• decrease of trabecular structures

abnormal articular cartilage morphology ( J:97992 )

• increased cartilage damage as denoted by widespread loss of proteoglycans in the articular cartilage compared with Tg(HBB-TNF)197Gkl mice

increased bone resorption ( J:97992 )

• massive increase in numbers of osteoclasts and osteoclast-covered surface

• increased serum parameters of bone resorption (cross-laps)

behavior/neurological

decreased grip strength ( J:97992 )

• grip strength of paws deteriorated significantly faster compared with Tg(HBB-TNF)197Gkl mice

immune system

abnormal osteoclast morphology ( J:97992 )

• increased size of osteoclasts compared with Tg(HBB-TNF)197Gkl mice

abnormal osteoclast differentiation ( J:97992 )

• more enhanced in vitro osteoclastogenesis in spleen cells in the presence of M-CSF and receptor activator of NF-kappaB ligand than cells in Tg(HBB-TNF)197Gkl mice

• extensive areas of bone resorption

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

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

• higher proliferative activity in osteoclasts

• reduced rate of apoptosis in osteoclasts

increased osteoclast cell number ( J:97992 )

• increased numbers of osteoclasts compared with Tg(HBB-TNF)197Gkl mice

increased circulating interleukin-1 level ( J:97992 )

• increased serum IL-1 level compared with Tg(HBB-TNF)197Gkl mice

increased circulating interleukin-6 level ( J:97992 )

• increased serum IL-6 level compared with Tg(HBB-TNF)197Gkl mice

increased interleukin-1 secretion ( J:97992 )

• increased production of IL-1 in osteoclasts compared with cells from Tg(HBB-TNF)197Gkl mice

increased interleukin-6 secretion ( J:97992 )

• increased production of IL-6 in osteoclasts compared with cells from Tg(HBB-TNF)197Gkl mice

arthritis ( J:97992 )

• arthritis at the age of 4 week

• disease activity is significantly enhanced and progress significantly faster compared with Tg(HBB-TNF)197Gkl mice

• larger areas of inflammatory bone erosions

hematopoietic system

abnormal osteoclast morphology ( J:97992 )

• increased size of osteoclasts compared with Tg(HBB-TNF)197Gkl mice

abnormal osteoclast differentiation ( J:97992 )

• more enhanced in vitro osteoclastogenesis in spleen cells in the presence of M-CSF and receptor activator of NF-kappaB ligand than cells in Tg(HBB-TNF)197Gkl mice

• extensive areas of bone resorption

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

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

• higher proliferative activity in osteoclasts

• reduced rate of apoptosis in osteoclasts

increased osteoclast cell number ( J:97992 )

• increased numbers of osteoclasts compared with Tg(HBB-TNF)197Gkl mice

homeostasis/metabolism

increased circulating interleukin-1 level ( J:97992 )

• increased serum IL-1 level compared with Tg(HBB-TNF)197Gkl mice

increased circulating interleukin-6 level ( J:97992 )

• increased serum IL-6 level compared with Tg(HBB-TNF)197Gkl mice

joint swelling ( J:97992 )

• progressive joint swelling

cellular

abnormal osteoclast differentiation ( J:97992 )

• more enhanced in vitro osteoclastogenesis in spleen cells in the presence of M-CSF and receptor activator of NF-kappaB ligand than cells in Tg(HBB-TNF)197Gkl mice

• extensive areas of bone resorption

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

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

• higher proliferative activity in osteoclasts

• reduced rate of apoptosis in osteoclasts

Genotype
MGI:3053718

tg3

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

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