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Phenotypes Associated with This Genotype
Genotype
MGI:3839558
Allelic
Composition
Tg(FCGR2A)11Mkz/Tg(FCGR2A)11Mkz
Genetic
Background
involves: C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(FCGR2A)11Mkz mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• sera IgG2a levels are elevated more than 2-fold in mice with severe spontaneous arthritis
• macrophages produce 6.5-fold more TNF in response to immunoglobulin aggregates compared to controls
• macrophages produce 6.5-fold more TNF in response to immunoglobulin aggregates compared to controls
• in mice over 20 weeks of age, 13 of 23 have anti-histone antibodies above background levels
• 32% of mice develop a spontaneous form of arthritis between 20 and 50 weeks of age
• arthritis is characterized by severe ankylosis of the tibiotarsal and tarsophalangeal cartilage, loss of joint space and prominent periarticular new bone formation
• the arthritic joints contain synovial hyperplasia and proliferation, cartilage erosion, pannus formation, and joint space infiltrate
• transgenic mice have an earlier onset of collagen-induced arthritis than controls despite having a protective H2 locus
• mean day of onset is 18 days versus 22 days in the susceptible DBA/1 strain
• 15% of mice develop arthritis with just one immunization of collagen compared to none in DBA/1 mice
• over 90% of mice develop arthritis within six days after a second injection of collagen compared to less then 10% of DBA/1 mice
• mice are also highly susceptible to an arthritis model initiated by injections of anti-collagen antibodies
• 100% of mice develop arthritis after injection of anti-collagen antibody while controls needed an LPS adjuvant in addition to the immunoglobulins to develop disease
• mice have an age-related progression to severe glomerulonephritis
• few mice have the disease prior to 20 weeks of age, up to 80% have disease by 40 weeks of age, and all mice have disease over 40 weeks of age
• disease is first evident as multifocallymphoplasmacytic infiltrate in the renal interstitium mainly around major arcuate vessels
• more advanced disease was seen, with enlarged glomeruli, increased mesangial matrix and condensation of glomerular tufts
• disease is self-limiting as kidney function is never impaired
• pneumonitis was found in 25% of mice between 12 to 40 weeks of age and increases to 100% in older mice
• disease is characterized by patches of perivascular inflammation with cellular aggregates of macrophages, lymphocytes, and plasma cells within alveolar walls
• in severe cases, up to 50% of the normal architecture of the lungs is obliterated

renal/urinary system
• mice have an age-related progression to severe glomerulonephritis
• few mice have the disease prior to 20 weeks of age, up to 80% have disease by 40 weeks of age, and all mice have disease over 40 weeks of age
• disease is first evident as multifocallymphoplasmacytic infiltrate in the renal interstitium mainly around major arcuate vessels
• more advanced disease was seen, with enlarged glomeruli, increased mesangial matrix and condensation of glomerular tufts
• disease is self-limiting as kidney function is never impaired
• immunoglobulin deposition is noted in the kidney

respiratory system
• pneumonitis was found in 25% of mice between 12 to 40 weeks of age and increases to 100% in older mice
• disease is characterized by patches of perivascular inflammation with cellular aggregates of macrophages, lymphocytes, and plasma cells within alveolar walls
• in severe cases, up to 50% of the normal architecture of the lungs is obliterated

skeleton
• 32% of mice develop a spontaneous form of arthritis between 20 and 50 weeks of age
• arthritis is characterized by severe ankylosis of the tibiotarsal and tarsophalangeal cartilage, loss of joint space and prominent periarticular new bone formation
• the arthritic joints contain synovial hyperplasia and proliferation, cartilage erosion, pannus formation, and joint space infiltrate
• transgenic mice have an earlier onset of collagen-induced arthritis than controls despite having a protective H2 locus
• mean day of onset is 18 days versus 22 days in the susceptible DBA/1 strain
• 15% of mice develop arthritis with just one immunization of collagen compared to none in DBA/1 mice
• over 90% of mice develop arthritis within six days after a second injection of collagen compared to less then 10% of DBA/1 mice
• mice are also highly susceptible to an arthritis model initiated by injections of anti-collagen antibodies
• 100% of mice develop arthritis after injection of anti-collagen antibody while controls needed an LPS adjuvant in addition to the immunoglobulins to develop disease

hematopoietic system
• sera IgG2a levels are elevated more than 2-fold in mice with severe spontaneous arthritis
• macrophages produce 6.5-fold more TNF in response to immunoglobulin aggregates compared to controls

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
rheumatoid arthritis DOID:7148 OMIM:180300
J:136516


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
04/09/2019
MGI 6.13
The Jackson Laboratory