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Phenotypes Associated with This Genotype
Genotype
MGI:5903775
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


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
04/23/2024
MGI 6.23
The Jackson Laboratory