Phenotypes associated with this allele

• Allele Symbol: Tg(TcraS106-1,TcrbS106-1)TS1SWAjca
• Allele Name: transgene insertion TS1SW, Andrew J Caton
• Allele ID: MGI:5903429
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Igk^tm1Dhu/Igk^tm1Dhu Tg(H2-Ea-HA)HACIIAjca/0 Tg(TcraS106-1,TcrbS106-1)TS1SWAjca/0	C.Cg-Igk^tm1Dhu Tg(H2-Ea-HA)HACIIAjca Tg(TcraS106-1,TcrbS106-1)TS1SWAjca	MGI:5903780
cx2	Tg(H2-Ea-HA)HACIIAjca/0 Tg(TcraS106-1,TcrbS106-1)TS1SWAjca/0	C.Cg-Tg(H2-Ea-HA)HACIIAjca Tg(TcraS106-1,TcrbS106-1)TS1SWAjca	MGI:5903775

Genotype
MGI:5903780

cx1

• Allelic Composition: Igk^tm1Dhu/Igk^tm1Dhu; Tg(H2-Ea-HA)HACIIAjca/0; Tg(TcraS106-1,TcrbS106-1)TS1SWAjca/0
• Genetic Background: C.Cg-Igk^tm1Dhu Tg(H2-Ea-HA)HACIIAjca Tg(TcraS106-1,TcrbS106-1)TS1SWAjca

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

hematopoietic system

absent B cells ( J:209872 )

abnormal CD4-positive, alpha beta T cell morphology ( J:209872 )

• 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

increased CD4-positive, alpha-beta T cell number ( J:209872 )

• 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

abnormal spleen morphology ( J:209872 )

• decrease in the overall cellularity of spleens

immune system

absent B cells ( J:209872 )

abnormal CD4-positive, alpha beta T cell morphology ( J:209872 )

• 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

increased CD4-positive, alpha-beta T cell number ( J:209872 )

• 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

abnormal spleen morphology ( J:209872 )

• decrease in the overall cellularity of spleens

abnormal lymph node morphology ( J:209872 )

• decrease in the overall cellularity of the joint-draining lymph nodes

decreased susceptibility to autoimmune disorder ( J:209872 )

• mice exhibit decreased arthritis development compared to double Tg(Tcra/Tcrb)#Ajca/0 Tg(H2-Ea-HA)#Ajca/0 transgenic mice

Genotype
MGI:5903775

cx2

• 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

hematopoietic system

abnormal CD4-positive, alpha beta T cell morphology ( J:209872 )

• 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

increased IgG level ( J:209872 )

• 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

abnormal CD4-positive, alpha-beta T cell physiology ( J:209872 )

• CD4+ T cells undergo little or no proliferation response to APCs from these mice

homeostasis/metabolism

abnormal circulating cytokine level ( J:209872 )

• proinflammatory cytokine levels are decreased in serum of arthritic mice compared to single Tg(Tcra/Tcrb)#Ajca/0 mice

increased circulating interleukin-17 level ( J:209872 )

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

decreased circulating interleukin-6 level ( J:209872 )

• interleukin-6 levels are decreased in serum of arthritic mice compared to single Tg(Tcra/Tcrb)#Ajca/0 mice

immune system

immune system phenotype ( J:209872 )

N • perivascular infiltrates are not seen in the lungs of arthritic mice and no inflammation in the hearts and kidneys

abnormal CD4-positive, alpha beta T cell morphology ( J:209872 )

• 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

increased IgG level ( J:209872 )

• 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

abnormal CD4-positive, alpha-beta T cell physiology ( J:209872 )

• CD4+ T cells undergo little or no proliferation response to APCs from these mice

abnormal circulating cytokine level ( J:209872 )

• proinflammatory cytokine levels are decreased in serum of arthritic mice compared to single Tg(Tcra/Tcrb)#Ajca/0 mice

increased circulating interleukin-17 level ( J:209872 )

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

decreased circulating interleukin-6 level ( J:209872 )

• interleukin-6 levels are decreased in serum of arthritic mice compared to single Tg(Tcra/Tcrb)#Ajca/0 mice

enlarged lymph nodes ( J:209872 )

• joint-draining lymph nodes of arthritic females are larger than either arthritic or nonarthritic males

joint inflammation ( J:209872 )

• swollen joints show a high degree of synovitis

• males show lower synovitis and articular degeneration than females

arthritis ( J:209872 )

• 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

joint inflammation ( J:209872 )

• swollen joints show a high degree of synovitis

• males show lower synovitis and articular degeneration than females

arthritis ( J:209872 )

• 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

abnormal articular cartilage morphology ( J:209872 )

• 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