Phenotypes associated with this allele

• Allele Symbol: Tg(FCGR2A)11Mkz
• Allele Name: transgene insertion 11, Steven E McKenzie
• Allele ID: MGI:3056729
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Del(1Fcgr2b-Fcgr3)1Rav/Del(1Fcgr2b-Fcgr3)1Rav Fcgr1^tm1Hoga/Fcgr1^tm1Hoga Tg(FCGR1A)#Jgjw/0 Tg(FCGR2A)11Mkz/0 Tg(FCGR2B)#Rav/0 Tg(FCGR3A)1156Rav/0 Tg(FCGR3B)1373Rav/0	involves: 129S1/Sv * C57BL/6 * CBA/Ca * FVB/N	MGI:5426844
cx2	Tg(FCGR2A)11Mkz/0 Tg(PF4)#Zcy/0	involves: C57BL/6 * SJL	MGI:4941606
tg3	Tg(FCGR2A)11Mkz/Tg(FCGR2A)11Mkz	involves: C57BL/6 * SJL	MGI:3839558
tg4	Tg(FCGR2A)11Mkz/0	involves: C57BL/6 * SJL	MGI:3839538

Genotype
MGI:5426844

cx1

• Allelic Composition: Del(1Fcgr2b-Fcgr3)1Rav/Del(1Fcgr2b-Fcgr3)1Rav; Fcgr1^tm1Hoga/Fcgr1^tm1Hoga; Tg(FCGR1A)#Jgjw/0; Tg(FCGR2A)11Mkz/0; Tg(FCGR2B)#Rav/0; Tg(FCGR3A)1156Rav/0; Tg(FCGR3B)1373Rav/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * CBA/Ca * FVB/N

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

normal phenotype

no abnormal phenotype detected ( J:183615 )

• mice are fertile, develop normally, generate normal immune responses and do not appear to have any evidence of spontaneous pathology

Genotype
MGI:4941606

cx2

• Allelic Composition: Tg(FCGR2A)11Mkz/0; Tg(PF4)#Zcy/0
• Genetic Background: involves: C57BL/6 * SJL

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:72220 )

• following treatment with KKO and heparin, 2 of 4 mice die unlike similarly treated single transgenic mice

hematopoietic system

thrombocytopenia ( J:72220 )

• following treatment with KKO and heparin

homeostasis/metabolism

increased susceptibility to induced thrombosis ( J:72220 )

• following treatment with KKO and heparin, mice exhibit fibrin thrombi in the arterioles and capillaries in the heart, liver, lungs, and kidney unlike similarly treated single transgenic mice

decreased body temperature ( J:72220 )

• following treatment with KKO and heparin

behavior/neurological

hunched posture ( J:72220 )

• following treatment with KKO and heparin

decreased locomotor activity ( J:72220 )

• following treatment with KKO and heparin

respiratory system

respiratory distress ( J:72220 )

• following treatment with KKO and heparin

immune system

increased acute inflammation ( J:72220 )

• following treatment with KKO and heparin, mice exhibit severe thrombopenia, decreased activity, rapid shallow breathing, hunched posture, and tactile hypothermia with increased lethality and fibrin thrombi in the arterioles and capillaries in the heart, liver, lungs, and kidney compared with similarly treated single transgenic mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
acquired thrombocytopenia		DOID:11126		J:72220

Genotype
MGI:3839558

tg3

• Allelic Composition: Tg(FCGR2A)11Mkz/Tg(FCGR2A)11Mkz
• Genetic Background: involves: C57BL/6 * SJL

immune system

increased IgG2a level ( J:136516 )

• sera IgG2a levels are elevated more than 2-fold in mice with severe spontaneous arthritis

abnormal macrophage physiology ( J:136516 )

• macrophages produce 6.5-fold more TNF in response to immunoglobulin aggregates compared to controls

increased tumor necrosis factor secretion ( J:136516 )

• macrophages produce 6.5-fold more TNF in response to immunoglobulin aggregates compared to controls

increased anti-histone antibody level ( J:136516 )

• in mice over 20 weeks of age, 13 of 23 have anti-histone antibodies above background levels

autoimmune arthritis ( J:136516 )

• 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

increased susceptibility to induced arthritis ( J:136516 )

• 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

glomerulonephritis ( J:136516 )

• 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

interstitial pneumonia ( J:136516 )

• 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

glomerulonephritis ( J:136516 )

• 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

renal glomerular immunoglobulin deposits ( J:136516 )

• immunoglobulin deposition is noted in the kidney

respiratory system

interstitial pneumonia ( J:136516 )

• 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

autoimmune arthritis ( J:136516 )

• 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

increased susceptibility to induced arthritis ( J:136516 )

• 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

increased IgG2a level ( J:136516 )

• sera IgG2a levels are elevated more than 2-fold in mice with severe spontaneous arthritis

abnormal macrophage physiology ( J:136516 )

• 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

Genotype
MGI:3839538

tg4

• Allelic Composition: Tg(FCGR2A)11Mkz/0
• Genetic Background: involves: C57BL/6 * SJL

hematopoietic system

abnormal platelet morphology ( J:93244 )

• severe thrombocytopenia can be induced in mice by an anti-platelet rat monoclonal antibody specific for platelets that normally induces only a mild thrombocytopenia in wild-type mice