Phenotypes associated with this allele

• Allele Symbol: Tg(TcraR28,TcrbR28)KRNDim
• Allele Name: transgene insertion KRN, Diane Mathis
• Allele ID: MGI:3767242
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Ighm^tm1Cgn/Ighm^tm1Cgn Tg(TcraR28,TcrbR28)KRNDim/0	involves: 129S2/SvPas * C57BL/6 * NOD * SJL	MGI:3842821
cx2	Ido2^em1Lamn/Ido2^em1Lamn Tg(TcraR28,TcrbR28)KRNDim/0	involves: C57BL/6 * C57BL/6J * SJL	MGI:7579160
cx3	Ido2^em2Lamn/Ido2^em2Lamn Tg(TcraR28,TcrbR28)KRNDim/0	involves: C57BL/6 * C57BL/6J * SJL	MGI:7579163
cx4	H2^b/H2^g7 Tg(TcraR28,TcrbR28)KRNDim/0	involves: C57BL/6 * NOD * SJL	MGI:3842820
tg5	Tg(TcraR28,TcrbR28)KRNDim/0	involves: C57BL/6 * NOD * SJL	MGI:3842819

Genotype
MGI:3842821

cx1

• Allelic Composition: Ighm^tm1Cgn/Ighm^tm1Cgn; Tg(TcraR28,TcrbR28)KRNDim/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * NOD * SJL

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

immune system

immune system phenotype ( J:36815 )

N • arthritis does not occur in these mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
NOT	rheumatoid arthritis	DOID:7148	OMIM:180300	J:36815

Genotype
MGI:7579160

cx2

• Allelic Composition: Ido2^em1Lamn/Ido2^em1Lamn; Tg(TcraR28,TcrbR28)KRNDim/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * SJL

immune system

autoimmune arthritis ( J:342726 )

• extensive immune cell infiltration, synovial hyperplasia and cartilage erosion

skeleton

autoimmune arthritis ( J:342726 )

• extensive immune cell infiltration, synovial hyperplasia and cartilage erosion

Genotype
MGI:7579163

cx3

• Allelic Composition: Ido2^em2Lamn/Ido2^em2Lamn; Tg(TcraR28,TcrbR28)KRNDim/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * SJL

immune system

autoimmune arthritis ( J:342726 )

• delayed onset and reduced severity of arthritis: reduced immune cell infiltration, synovial hyperplasia and cartilage erosion

skeleton

autoimmune arthritis ( J:342726 )

• delayed onset and reduced severity of arthritis: reduced immune cell infiltration, synovial hyperplasia and cartilage erosion

Genotype
MGI:3842820

cx4

• Allelic Composition: H2^b/H2^g7; Tg(TcraR28,TcrbR28)KRNDim/0
• Genetic Background: involves: C57BL/6 * NOD * SJL

immune system

mitral valve inflammation ( J:275827 )

• mitral valve inflammation begins at 3 weeks of age and by 8 weeks, accumulation of inflammatory cells and interstitial thickening is obvious indicating fibroinflammatory mitral valve disease

• mononuclear phagocytes (macrophages and monocytes) constitute the vast majority of accumulated leukocytes

• frequency of TNF- and IL-6-producing phagocytes in inflamed mitral valve tissue is elevated, indicating an enrichment of cytokine-producing phagocytes within the inflamed mitral valves

• antibody blockade of either TNF or IL-6 beginning at the onset of mitral valve inflammation reduces mitral valve fibrosis and thickening

rheumatoid arthritis ( J:36815 , J:275827 )

• rheumatoid arthritis occurs with disease onset transpiring between 25 and 35 days of age (J:36815)

• arthritis occurrence is established by joint inspection and measure of ankle thickness, and histological confirmation in several mice (J:36815)

cardiovascular system

abnormal mitral valve morphology ( J:275827 )

• mitral valve hydroxyproline content is elevated

thick mitral valve ( J:275827 )

• by 8 weeks of age, mitral valves are fibrotic and thickened

• TNFR2 neutralization with a monoclonal antibody exacerbates mitral valve fibrosis and thickening

• blockade of either VLA-4 or VCAM-1 with monoclonal antibodies attenuates valve fibrosis and thickening

mitral valve inflammation ( J:275827 )

• mitral valve inflammation begins at 3 weeks of age and by 8 weeks, accumulation of inflammatory cells and interstitial thickening is obvious indicating fibroinflammatory mitral valve disease

• mononuclear phagocytes (macrophages and monocytes) constitute the vast majority of accumulated leukocytes

• frequency of TNF- and IL-6-producing phagocytes in inflamed mitral valve tissue is elevated, indicating an enrichment of cytokine-producing phagocytes within the inflamed mitral valves

• antibody blockade of either TNF or IL-6 beginning at the onset of mitral valve inflammation reduces mitral valve fibrosis and thickening

homeostasis/metabolism

increased hydroxyproline level ( J:275827 )

• mitral valve hydroxyproline content is elevated

skeleton

rheumatoid arthritis ( J:36815 , J:275827 )

• rheumatoid arthritis occurs with disease onset transpiring between 25 and 35 days of age (J:36815)

• arthritis occurrence is established by joint inspection and measure of ankle thickness, and histological confirmation in several mice (J:36815)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
mitral valve disease		DOID:61		J:275827
rheumatoid arthritis		DOID:7148	OMIM:180300	J:36815

Genotype
MGI:3842819

tg5

• Allelic Composition: Tg(TcraR28,TcrbR28)KRNDim/0
• Genetic Background: involves: C57BL/6 * NOD * SJL

immune system

abnormal macrophage chemotaxis ( J:36815 )

• macrophage cells make up a large number of cells found in inflamed joints

enlarged spleen ( J:36815 )

• splenomegaly is often observed

abnormal T cell clonal deletion ( J:36815 )

• single-positive populations normalize by 4 weeks of age though total cell numbers are still reduced

• clonal deletion is evident in the thymus of neonatal mice with reduced numbers of total cells and aberrant percentages of single-positive populations

• clonal deletion affects T cell populations in the periphery with a paucity of single-positive T cells in young mice and chronically reduced CD4⁺ population in adults

abnormal lymphocyte cell number ( J:36815 )

increased B cell number ( J:36815 )

• spleen and lymph node B cell numbers are increased 1.75-fold in mice suffering from arthritis

decreased CD4-positive, alpha-beta T cell number ( J:36815 )

• CD4⁺ T cells are virtually absent in the spleens of mice under 2 weeks of age

• CD4⁺ T cell numbers are reduced by 3.1-fold in the spleens of adult mice

decreased CD8-positive, alpha-beta T cell number ( J:36815 )

• CD8 ⁺T cells numbers are reduced in mice under 3 weeks of age

impaired neutrophil recruitment ( J:36815 )

• neutrophils make up a large number of cells found in inflamed joints

increased IgG1 level ( J:36815 )

• serum IgG1 levels are dramatically increased

abnormal T cell activation ( J:36815 )

• a greater proportion of T cells express late activation markers (CD44^hi CD62L^lo, CD45RB^lo) than in transgene negative controls

abnormal T cell proliferation ( J:36815 )

• T cells expressing the transgenic TCR proliferate in response to antigen presenting cells expressing Class II MHC from a H2^g7 locus in the absence of any antigen

abnormal T cell anergy ( J:36815 )

• Background Sensitivity: transgenic T cells from mice on a NOD background have lower levels of T cell receptor expressed

• Background Sensitivity: transgenic T cells from mice on a NOD background have a severe reduction in response to its cognate antigen (RNAse peptide) presented by A^k than do transgenic T cells from a C57BL/6 background

• hybridomas created from these T cells respond normally to antigen suggesting a cell intrinsic anergy

rheumatoid arthritis ( J:36815 )

• Background Sensitivity: transgenic mice crossed to a NOD background develop rheumatoid arthritis

• distal paws become red and swollen

• all transgenic mice have significantly swollen ankles by 30 days of age with the degree of swelling symmetrical on either limb

• as mice age hyperextension of the ankle, valgus deviation of the knee and hyperpronation of the toes occur

• arthritis occurs in almost all joints with the exception of hip joints

• arthritis starts as fibrinoid material and a few cells are found in the articular cavity; edema sets in under the synovial lining, accompanied by neovascularithezation and some infiltration of inflammatory cells

• after a few weeks, disease is marked by extensive synovitis, affecting all areas of the joint with massive infiltration of inflammatory cells and beginnings of fibrosis

• after several months, the inflammation recedes leaving massive fibrosis, very little cartilage, and irregular shaped bone

chronic joint inflammation ( J:36815 )

• occurs as part of arthritis disease process

kidney inflammation ( J:36815 )

• immunoglobulin deposits occur along the peritubular basal membranes in the cortex and medulla

glomerulonephritis ( J:36815 )

• immunoglobulin deposits are detected in the glomeruli

limbs/digits/tail

abnormal phalanx morphology ( J:36815 )

• bones are eroded from arthritis with anarchic reconstruction occurring afterwards

clinodactyly ( J:36815 )

• rheumatoid arthritis leads to hyperpronation of the toes

abnormal metatarsal bone morphology ( J:36815 )

• bones are eroded from arthritis with anarchic reconstruction occurring afterwards

skeleton

rheumatoid arthritis ( J:36815 )

• Background Sensitivity: transgenic mice crossed to a NOD background develop rheumatoid arthritis

• distal paws become red and swollen

• all transgenic mice have significantly swollen ankles by 30 days of age with the degree of swelling symmetrical on either limb

• as mice age hyperextension of the ankle, valgus deviation of the knee and hyperpronation of the toes occur

• arthritis occurs in almost all joints with the exception of hip joints

• arthritis starts as fibrinoid material and a few cells are found in the articular cavity; edema sets in under the synovial lining, accompanied by neovascularithezation and some infiltration of inflammatory cells

• after a few weeks, disease is marked by extensive synovitis, affecting all areas of the joint with massive infiltration of inflammatory cells and beginnings of fibrosis

• after several months, the inflammation recedes leaving massive fibrosis, very little cartilage, and irregular shaped bone

chronic joint inflammation ( J:36815 )

• occurs as part of arthritis disease process

abnormal phalanx morphology ( J:36815 )

• bones are eroded from arthritis with anarchic reconstruction occurring afterwards

abnormal metatarsal bone morphology ( J:36815 )

• bones are eroded from arthritis with anarchic reconstruction occurring afterwards

abnormal intervertebral disk morphology ( J:36815 )

• intervertebral inflammation occurs sporadically in these mice

decreased joint mobility ( J:36815 )

• mobility is compromised due to arthritis

renal/urinary system

kidney inflammation ( J:36815 )

• immunoglobulin deposits occur along the peritubular basal membranes in the cortex and medulla

glomerulonephritis ( J:36815 )

• immunoglobulin deposits are detected in the glomeruli

renal glomerular immunoglobulin deposits ( J:36815 )

hematopoietic system

abnormal macrophage chemotaxis ( J:36815 )

• macrophage cells make up a large number of cells found in inflamed joints

enlarged spleen ( J:36815 )

• splenomegaly is often observed

abnormal T cell clonal deletion ( J:36815 )

• clonal deletion is evident in the thymus of neonatal mice with reduced numbers of total cells and aberrant percentages of single-positive populations

• single-positive populations normalize by 4 weeks of age though total cell numbers are still reduced

• clonal deletion affects T cell populations in the periphery with a paucity of single-positive T cells in young mice and chronically reduced CD4⁺ population in adults

abnormal lymphocyte cell number ( J:36815 )

increased B cell number ( J:36815 )

• spleen and lymph node B cell numbers are increased 1.75-fold in mice suffering from arthritis

decreased CD4-positive, alpha-beta T cell number ( J:36815 )

• CD4⁺ T cells are virtually absent in the spleens of mice under 2 weeks of age

• CD4⁺ T cell numbers are reduced by 3.1-fold in the spleens of adult mice

decreased CD8-positive, alpha-beta T cell number ( J:36815 )

• CD8 ⁺T cells numbers are reduced in mice under 3 weeks of age

impaired neutrophil recruitment ( J:36815 )

• neutrophils make up a large number of cells found in inflamed joints

increased IgG1 level ( J:36815 )

• serum IgG1 levels are dramatically increased

abnormal T cell activation ( J:36815 )

• a greater proportion of T cells express late activation markers (CD44^hi CD62L^lo, CD45RB^lo) than in transgene negative controls

abnormal T cell proliferation ( J:36815 )

• T cells expressing the transgenic TCR proliferate in response to antigen presenting cells expressing Class II MHC from a H2^g7 locus in the absence of any antigen

cellular

abnormal macrophage chemotaxis ( J:36815 )

• macrophage cells make up a large number of cells found in inflamed joints

abnormal T cell proliferation ( J:36815 )

• T cells expressing the transgenic TCR proliferate in response to antigen presenting cells expressing Class II MHC from a H2^g7 locus in the absence of any antigen

growth/size/body

enlarged spleen ( J:36815 )

• splenomegaly is often observed

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
rheumatoid arthritis		DOID:7148	OMIM:180300	J:36815