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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Tg(H2-Ea-HA)HACIIAjca
transgene insertion HACII, Andrew J Caton
MGI:5903427
Summary 4 genotypes


Genotype
MGI:5903778
cx1
Allelic
Composition
Igktm1Dhu/Igktm1Dhu
Tg(H2-Ea-HA)HACIIAjca/0
Tg(Tcra/Tcrb)1Vbo/0
Genetic
Background
C.Cg-Igktm1Dhu Tg(H2-Ea-HA)HACIIAjca Tg(Tcra/Tcrb)1Vbo
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Igktm1Dhu mutation (1 available); any Igk mutation (25 available)
Tg(H2-Ea-HA)HACIIAjca mutation (1 available)
Tg(Tcra/Tcrb)1Vbo mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• mice develop arthritis more quickly but with disease penetrance and severity similar to double Tg(Tcra/Tcrb)1Vbo/0 Tg(H2-Ea-HA)#Ajca/0 transgenic mice

skeleton
• mice develop arthritis more quickly but with disease penetrance and severity similar to double Tg(Tcra/Tcrb)1Vbo/0 Tg(H2-Ea-HA)#Ajca/0 transgenic mice




Genotype
MGI:5903780
cx2
Allelic
Composition
Igktm1Dhu/Igktm1Dhu
Tg(H2-Ea-HA)HACIIAjca/0
Tg(TcraS106-1,TcrbS106-1)TS1SWAjca/0
Genetic
Background
C.Cg-Igktm1Dhu Tg(H2-Ea-HA)HACIIAjca Tg(TcraS106-1,TcrbS106-1)TS1SWAjca
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Igktm1Dhu mutation (1 available); any Igk mutation (25 available)
Tg(H2-Ea-HA)HACIIAjca mutation (1 available)
Tg(TcraS106-1,TcrbS106-1)TS1SWAjca mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
• decrease in the percentages of IL-17- and IFN-gamma-secreting Valpha8.3+VBeta10+ CD4+T cells in the joint-draining lymph nodes of nonarthritic mice
• in mice that develop arthritis despite absence of B cells, the frequencies of IFN-gamma-secreting Valpha8.3+VBeta10+ CD4+T are reduced relative to arthritic double Tg(Tcra/Tcrb)#Ajca/0 Tg(H2-Ea-HA)#Ajca/0 transgenic mice, but the frequencies of IL-17-secreting Valpha8.3+VBeta10+CD4+ T cells are not
• nonarthritic mice show lower frequencies of clonotypic, but not of total, IFN-gamma-, and IL-17 producing CD4+ T cells than nonarthritic double Tg(Tcra/Tcrb)#Ajca/0 Tg(H2-Ea-HA)#Ajca/0 transgenic mice
• percentage of CD4+ T cells is increased, however the number of CD4+ T cells expressing the Vslpha8.3+Vbeta10+ clonotypic TCR does not differ from double Tg(Tcra/Tcrb)#Ajca/0 Tg(H2-Ea-HA)#Ajca/0 transgenic mice
• decrease in the overall cellularity of spleens

immune system
• decrease in the percentages of IL-17- and IFN-gamma-secreting Valpha8.3+VBeta10+ CD4+T cells in the joint-draining lymph nodes of nonarthritic mice
• in mice that develop arthritis despite absence of B cells, the frequencies of IFN-gamma-secreting Valpha8.3+VBeta10+ CD4+T are reduced relative to arthritic double Tg(Tcra/Tcrb)#Ajca/0 Tg(H2-Ea-HA)#Ajca/0 transgenic mice, but the frequencies of IL-17-secreting Valpha8.3+VBeta10+CD4+ T cells are not
• nonarthritic mice show lower frequencies of clonotypic, but not of total, IFN-gamma-, and IL-17 producing CD4+ T cells than nonarthritic double Tg(Tcra/Tcrb)#Ajca/0 Tg(H2-Ea-HA)#Ajca/0 transgenic mice
• percentage of CD4+ T cells is increased, however the number of CD4+ T cells expressing the Vslpha8.3+Vbeta10+ clonotypic TCR does not differ from double Tg(Tcra/Tcrb)#Ajca/0 Tg(H2-Ea-HA)#Ajca/0 transgenic mice
• decrease in the overall cellularity of spleens
• decrease in the overall cellularity of the joint-draining lymph nodes
• mice exhibit decreased arthritis development compared to double Tg(Tcra/Tcrb)#Ajca/0 Tg(H2-Ea-HA)#Ajca/0 transgenic mice




Genotype
MGI:5903489
cx3
Allelic
Composition
Tg(H2-Ea-HA)HACIIAjca/0
Tg(Tcra/Tcrb)1Vbo/0
Genetic
Background
C.Cg-Tg(H2-Ea-HA)HACIIAjca Tg(Tcra/Tcrb)1Vbo
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(H2-Ea-HA)HACIIAjca mutation (1 available)
Tg(Tcra/Tcrb)1Vbo mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• mild inflammatory processes are seen in the hearts of some arthritic mice
• severe deletion of HA-specific 6.5+CD4+CD8- single-positive thymocytes indicating deletion of autoreactive CD4+ T cells, although a subset of 6.5+CD4+ T cells evades deletion and accumulates in spleens and lymph nodes
• modest increase in the percentages of CD4+CD8- Foxp3+ thymocytes and of CD4+Foxp3+ splenocytes, however, the numbers of these cells that express the clonotypic TS1 TCR are reduced, reflecting severe deletion of clonotype-expressing thymocytes
• increase in frequency of IL-17-secreting CD4+ T cells in the joint-draining lymph nodes and spleens of arthritic mice
• arthritic mice exhibit a higher level of serum IgG than control Tg(Tcra/Tcrb)1Vbo/0 mice
• proinflammatory cytokine levels are increased in serum of arthritic mice compared to single Tg(Tcra/Tcrb)1Vbo/0 mice
• interleukin-6 levels are increased in serum of arthritic mice compared to single Tg(Tcra/Tcrb)1Vbo/0 mice
• swollen joints show a high degree of synovitis
• majority of mice spontaneously develop inflammatory arthritis, showing overt joint inflammation and swelling affecting both front and rear paws
• joint inflammation first becomes evident between 6 and 8 weeks of age, and by 14 weeks almost all mice show at least one inflamed paw
• penetrance of arthritis is similar in males and females
• inflammatory arthritis develops in mice despite substantial deletion of autoreactive CD4+ T cells and despite the formation of Foxp3+ Tregs
• treatment of prearthritic mice with anti-TNF antibody results in a reduction in arthritis penetrance associated with a reduced accumulation of Th17 cells in the joints but has no effect on CD4+Foxp3+ Tregs
• mild inflammatory processes are seen in the kidneys of some arthritic mice

hematopoietic system
• severe deletion of HA-specific 6.5+CD4+CD8- single-positive thymocytes indicating deletion of autoreactive CD4+ T cells, although a subset of 6.5+CD4+ T cells evades deletion and accumulates in spleens and lymph nodes
• modest increase in the percentages of CD4+CD8- Foxp3+ thymocytes and of CD4+Foxp3+ splenocytes, however, the numbers of these cells that express the clonotypic TS1 TCR are reduced, reflecting severe deletion of clonotype-expressing thymocytes
• increase in frequency of IL-17-secreting CD4+ T cells in the joint-draining lymph nodes and spleens of arthritic mice
• arthritic mice exhibit a higher level of serum IgG than control Tg(Tcra/Tcrb)1Vbo/0 mice

homeostasis/metabolism
• proinflammatory cytokine levels are increased in serum of arthritic mice compared to single Tg(Tcra/Tcrb)1Vbo/0 mice
• interleukin-6 levels are increased in serum of arthritic mice compared to single Tg(Tcra/Tcrb)1Vbo/0 mice

cardiovascular system
• mild inflammatory processes are seen in the hearts of some arthritic mice

renal/urinary system
• mild inflammatory processes are seen in the kidneys of some arthritic mice

respiratory system
• extensive perivascular infiltrates in the lungs of arthritic mice

skeleton
• swollen joints show a high degree of synovitis
• majority of mice spontaneously develop inflammatory arthritis, showing overt joint inflammation and swelling affecting both front and rear paws
• joint inflammation first becomes evident between 6 and 8 weeks of age, and by 14 weeks almost all mice show at least one inflamed paw
• penetrance of arthritis is similar in males and females
• inflammatory arthritis develops in mice despite substantial deletion of autoreactive CD4+ T cells and despite the formation of Foxp3+ Tregs
• treatment of prearthritic mice with anti-TNF antibody results in a reduction in arthritis penetrance associated with a reduced accumulation of Th17 cells in the joints but has no effect on CD4+Foxp3+ Tregs
• swollen joints show a high degree of articular degeneration

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
arthritis DOID:848 J:209872




Genotype
MGI:5903775
cx4
Allelic
Composition
Tg(H2-Ea-HA)HACIIAjca/0
Tg(TcraS106-1,TcrbS106-1)TS1SWAjca/0
Genetic
Background
C.Cg-Tg(H2-Ea-HA)HACIIAjca Tg(TcraS106-1,TcrbS106-1)TS1SWAjca
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(H2-Ea-HA)HACIIAjca mutation (1 available)
Tg(TcraS106-1,TcrbS106-1)TS1SWAjca mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
• deletion of HA-specific Valpha8.3+CD4+CD8- thymocytes indicates deletion of autoreactive CD4+ T cells, although a subset of clonotypic CD4+ T cells evades deletion and accumulates in spleens and lymph nodes
• modest increase in the percentages of CD4+CD8- Foxp3+ thymocytes and of CD4+Foxp3+ splenocytes, however, the numbers of these cells that express the clonotypic TS1(SW) TCR are reduced, reflecting severe deletion of clonotype-expressing thymocytes
• however, no differences between males and females is seen in the percentages of CD4+ T cells, of CD4+CD25+Foxp3+ cells, of CD4+IL-17+ cells, or of B cells in the joint-draining lymph nodesincrease in frequency of IL-17-secreting CD4+ T cells in the joint-draining lymph nodes and spleens of arthritic mice
• 5-6 week old mice treated with an anti-CD20 mAb to eliminate B cells exhibit reduced spleen and joint-draining lymph node cellularities and increased percentages of CD4+ T cells
• treatment with an anti-CD20 mAb results in lower frequencies of clonotypic cytokine-producing T cells in mice that do not develop arthritis
• arthritic mice exhibit a higher level of serum IgG than control Tg(Tcra/Tcrb)#/0 mice
• serum IgG titers are highest in arthritic females and are lower in both arthritic and nonarthritic males
• 5-6 week old mice treated with an anti-CD20 mAb to eliminate B cells show reduced levels of serum IgG
• CD4+ T cells undergo little or no proliferation response to APCs from these mice

homeostasis/metabolism
• proinflammatory cytokine levels are decreased in serum of arthritic mice compared to single Tg(Tcra/Tcrb)#Ajca/0 mice
• interleukin-17 levels are higher in the serum of arthritic mice compared to single Tg(Tcra/Tcrb)#Ajca/0 mice
• interleukin-6 levels are decreased in serum of arthritic mice compared to single Tg(Tcra/Tcrb)#Ajca/0 mice

immune system
N
• perivascular infiltrates are not seen in the lungs of arthritic mice and no inflammation in the hearts and kidneys
• deletion of HA-specific Valpha8.3+CD4+CD8- thymocytes indicates deletion of autoreactive CD4+ T cells, although a subset of clonotypic CD4+ T cells evades deletion and accumulates in spleens and lymph nodes
• modest increase in the percentages of CD4+CD8- Foxp3+ thymocytes and of CD4+Foxp3+ splenocytes, however, the numbers of these cells that express the clonotypic TS1(SW) TCR are reduced, reflecting severe deletion of clonotype-expressing thymocytes
• however, no differences between males and females is seen in the percentages of CD4+ T cells, of CD4+CD25+Foxp3+ cells, of CD4+IL-17+ cells, or of B cells in the joint-draining lymph nodesincrease in frequency of IL-17-secreting CD4+ T cells in the joint-draining lymph nodes and spleens of arthritic mice
• 5-6 week old mice treated with an anti-CD20 mAb to eliminate B cells exhibit reduced spleen and joint-draining lymph node cellularities and increased percentages of CD4+ T cells
• treatment with an anti-CD20 mAb results in lower frequencies of clonotypic cytokine-producing T cells in mice that do not develop arthritis
• arthritic mice exhibit a higher level of serum IgG than control Tg(Tcra/Tcrb)#/0 mice
• serum IgG titers are highest in arthritic females and are lower in both arthritic and nonarthritic males
• 5-6 week old mice treated with an anti-CD20 mAb to eliminate B cells show reduced levels of serum IgG
• CD4+ T cells undergo little or no proliferation response to APCs from these mice
• proinflammatory cytokine levels are decreased in serum of arthritic mice compared to single Tg(Tcra/Tcrb)#Ajca/0 mice
• interleukin-17 levels are higher in the serum of arthritic mice compared to single Tg(Tcra/Tcrb)#Ajca/0 mice
• interleukin-6 levels are decreased in serum of arthritic mice compared to single Tg(Tcra/Tcrb)#Ajca/0 mice
• joint-draining lymph nodes of arthritic females are larger than either arthritic or nonarthritic males
• swollen joints show a high degree of synovitis
• males show lower synovitis and articular degeneration than females
• adult mice develop overt joint swelling affecting both front and hind paws
• males exhibit a lower penetrance of arthritis, a delay in disease onset, and decreased severity of arthritis relative to females
• mice that do not show overt joint swelling do not exhibit synovitis or articular degeneration
• inflammatory arthritis develops in mice despite substantial deletion of autoreactive CD4+ T cells and despite the formation of Foxp3+ Tregs
• treatment with an anti-IL-17R mAb abrogates arthritis development in females
• 5-6 week old mice treated with an anti-CD20 mAb to eliminate B cells prevents arthritis development in the majority of mice

skeleton
• swollen joints show a high degree of synovitis
• males show lower synovitis and articular degeneration than females
• adult mice develop overt joint swelling affecting both front and hind paws
• males exhibit a lower penetrance of arthritis, a delay in disease onset, and decreased severity of arthritis relative to females
• mice that do not show overt joint swelling do not exhibit synovitis or articular degeneration
• inflammatory arthritis develops in mice despite substantial deletion of autoreactive CD4+ T cells and despite the formation of Foxp3+ Tregs
• treatment with an anti-IL-17R mAb abrogates arthritis development in females
• 5-6 week old mice treated with an anti-CD20 mAb to eliminate B cells prevents arthritis development in the majority of mice
• swollen joints show a high degree of articular degeneration
• males show lower synovitis and articular degeneration than females

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
arthritis DOID:848 J:209872





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last database update
04/30/2024
MGI 6.23
The Jackson Laboratory