Phenotypes associated with this allele

• Allele Symbol: Tg(TcraBDC2.5,TcrbBDC2.5)1Doi
• Allele Name: transgene insertion 1, Christophe Benoist
• Allele ID: MGI:2181203
• Summary: 12 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm Tg(Cd4-cre)1Cwi/0 Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0	involves: 129 * C57BL/6 * DBA/2 * NOD * SJL	MGI:5514241
cn2	Ifng^tm1Ts/Ifng^tm1Ts Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0 Tg(Cd4-cre)1Cwi/0	involves: 129 * C57BL/6 * DBA/2 * NOD * SJL	MGI:5514242
cn3	Tgfb1^tm3.1Flv/Tgfb1^tm3.1Flv Tg(Cd4-cre)1Cwi/0 Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0	involves: 129 * C57BL/6 * DBA/2 * NOD * SJL	MGI:5514237
cn4	Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm Tnfrsf4^tm2(cre)Nik/Tnfrsf4^+ Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0	involves: 129 * C57BL/6 * NOD * SJL	MGI:5514245
cn5	Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm Tg(Foxp3-EGFP/cre)1cJbs/0 Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0	involves: 129S6/SvEvTac * C57BL/6 * NOD * SJL	MGI:5514247
cx6	H2^g7/H2^g7 Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0	B6.Cg-H2^g7 Tg(TcraBDC2.5,TcrbBDC2.5)1Doi	MGI:3640480
cx7	Ctla4^tm1All/Ctla4^tm1All Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * NOD * SJL	MGI:4940108
cx8	H2^g7/H2^g7 Tg(Ins2-Vtcn1)#Xxz/0 Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0	involves: C57BL/6 * NOD * SJL	MGI:5463746
cx9	Il4^tm1Cgn/Il4^tm1Cgn Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0	NOD.Cg-Il4^tm1Cgn Tg(TcraBDC2.5,TcrbBDC2.5)1Doi	MGI:3625063
cx10	Mertk^tm1Gkm/Mertk^tm1Gkm Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0	NOD.Cg-Mertk^tm1Gkm Tg(TcraBDC2.5,TcrbBDC2.5)1Doi	MGI:3844820
tg11	Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0	involves: C57BL/6 * NOD * SJL	MGI:3790786
tg12	Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0	NOD.Cg-Tg(TcraBDC2.5,TcrbBDC2.5)1Doi	MGI:3622335

Genotype
MGI:5514241

cn1

• Allelic Composition: Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm; Tg(Cd4-cre)1Cwi/0; Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0
• Genetic Background: involves: 129 * C57BL/6 * DBA/2 * NOD * SJL

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

mortality/aging

mortality/aging ( J:196160 )

N • improved survival

immune system

immune system phenotype ( J:196160 )

N • absolute numbers of Th1 cells in the spleen is unchanged from controls

abnormal immune system morphology ( J:196160 )

decreased regulatory T cell number ( J:196160 )

• significant reduction in spleen and pancreas

• reduced peripheral cell numbers

increased regulatory T cell number ( J:196160 )

• percentage in pancreatic lymph nodes is increased

abnormal immune system organ morphology ( J:196160 )

abnormal spleen morphology ( J:196160 )

• total cellularity of the spleen is reduced in 3 week old diabetic mice

abnormal abdominal lymph node morphology ( J:196160 )

• total cellularity of pancreatic lymph nodes is reduced in 3 week old diabetic mice

abnormal immune system physiology ( J:196160 )

pancreas inflammation ( J:196160 )

• massive infiltration of leukocytes into Islets before diabetes develops

abnormal immune serum protein physiology ( J:196160 )

increased interferon-gamma secretion ( J:196160 )

• in pancreatic T cells

abnormal interleukin secretion ( J:196160 )

• decreased Il22 expression in pancreatic T cells

decreased interleukin-17 secretion ( J:196160 )

• decreased Il17a in pancreatic T cells

increased interleukin-2 secretion ( J:196160 )

• in pancreatic T cells

increased interleukin-21 secretion ( J:196160 )

• in pancreatic T cells

decreased interleukin-9 secretion ( J:196160 )

• in pancreatic T cells

increased susceptibility to autoimmune diabetes ( J:196160 )

• become diabetic between 14 and 21 days of age

endocrine/exocrine glands

pancreas inflammation ( J:196160 )

• massive infiltration of leukocytes into Islets before diabetes develops

hematopoietic system

decreased regulatory T cell number ( J:196160 )

• significant reduction in spleen and pancreas

• reduced peripheral cell numbers

increased regulatory T cell number ( J:196160 )

• percentage in pancreatic lymph nodes is increased

abnormal spleen morphology ( J:196160 )

• total cellularity of the spleen is reduced in 3 week old diabetic mice

Genotype
MGI:5514242

cn2

• Allelic Composition: Ifng^tm1Ts/Ifng^tm1Ts; Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm; Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0; Tg(Cd4-cre)1Cwi/0
• Genetic Background: involves: 129 * C57BL/6 * DBA/2 * NOD * SJL

mortality/aging

mortality/aging ( J:196160 )

N • improved survival

immune system

immune system phenotype ( J:196160 )

N • do not develop diabetes

Genotype
MGI:5514237

cn3

• Allelic Composition: Tgfb1^tm3.1Flv/Tgfb1^tm3.1Flv; Tg(Cd4-cre)1Cwi/0; Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0
• Genetic Background: involves: 129 * C57BL/6 * DBA/2 * NOD * SJL

immune system

increased T-helper 1 cell number ( J:196160 )

• significantly increased Th1 cell numbers in spleen and pancreatic lymph nodes

increased regulatory T cell number ( J:196160 )

• increased frequency of T reg in the thymus and pancreatic lymph nodes

• number of T reg cells in pancreatic lymph nodes is increased as well

increased susceptibility to autoimmune diabetes ( J:196160 )

• rapidly develop diabetes but with a low incidence

• slow kinetics of disease progression

hematopoietic system

increased T-helper 1 cell number ( J:196160 )

• significantly increased Th1 cell numbers in spleen and pancreatic lymph nodes

increased regulatory T cell number ( J:196160 )

• increased frequency of T reg in the thymus and pancreatic lymph nodes

• number of T reg cells in pancreatic lymph nodes is increased as well

Genotype
MGI:5514245

cn4

• Allelic Composition: Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm; Tnfrsf4^tm2(cre)Nik/Tnfrsf4⁺; Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0
• Genetic Background: involves: 129 * C57BL/6 * NOD * SJL

immune system

immune system phenotype ( J:196160 )

N • absolute number of T reg cells in the spleen and the pancreatic lymph nodes are normal

increased susceptibility to autoimmune diabetes ( J:196160 )

• development of diabetes is somewhat delayed

Genotype
MGI:5514247

cn5

• Allelic Composition: Tgfbr2^tm1.2Hlm/Tgfbr2^tm1.2Hlm; Tg(Foxp3-EGFP/cre)1cJbs/0; Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * NOD * SJL

immune system

immune system phenotype ( J:196160 )

N • mice do not develop diabetes

N • normal T reg numbers in the spleen and pancreatic lymph nodes

increased regulatory T cell number ( J:196160 )

• in the thymus

hematopoietic system

increased regulatory T cell number ( J:196160 )

• in the thymus

Genotype
MGI:3640480

cx6

• Allelic Composition: H2^g7/H2^g7; Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0
• Genetic Background: B6.Cg-H2^g7 Tg(TcraBDC2.5,TcrbBDC2.5)1Doi

immune system

decreased susceptibility to autoimmune diabetes ( J:86926 )

• animals show a significant reduction in overall diabetes incidence (14.6% vs ~50% in Tnfsf4-heterozygotes and wild-type) and increase in the age of onset (9.5 weeks vs 6 weeks in controls)

• mice are considered diabetic after a blood glucose measure of >300 mg/dl and 2 positive urine glucose tests

Genotype
MGI:4940108

cx7

• Allelic Composition: Ctla4^tm1All/Ctla4^tm1All; Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * NOD * SJL

mortality/aging

mortality/aging ( J:109887 )

N • mice survive beyond 3 to 4 weeks of age unlike Ctla4^tm1All homozygotes

immune system

insulitis ( J:109887 )

• splenocytes transferred into Tcra^tm1Mjo/Tcra^tm1Mjo Tg(TcraBDC2.5,TcrbBDC2.5)1Doi induce diabetes at a higher rate than when Ctla4^tm1All/Ctla4⁺ Tg(TcraBDC2.5,TcrbBDC2.5)1Doi splenocytes are used

enlarged spleen ( J:109887 )

abnormal splenocyte physiology ( J:109887 )

• splenocytes transferred into Tcra^tm1Mjo/Tcra^tm1Mjo Tg(TcraBDC2.5,TcrbBDC2.5)1Doi induce diabetes at a higher rate than when Ctla4^tm1All/Ctla4⁺ Tg(TcraBDC2.5,TcrbBDC2.5)1Doi splenocytes are used

increased acute inflammation ( J:109887 )

• at 6 weeks, mice exhibit infiltration in the pancreas and spleen unlike in wild-type mice

• however, infiltration is not as severe or extensive as in Ctla4^tm1All homozygotes

hematopoietic system

enlarged spleen ( J:109887 )

abnormal splenocyte physiology ( J:109887 )

• splenocytes transferred into Tcra^tm1Mjo/Tcra^tm1Mjo Tg(TcraBDC2.5,TcrbBDC2.5)1Doi induce diabetes at a higher rate than when Ctla4^tm1All/Ctla4⁺ Tg(TcraBDC2.5,TcrbBDC2.5)1Doi splenocytes are used

endocrine/exocrine glands

insulitis ( J:109887 )

• splenocytes transferred into Tcra^tm1Mjo/Tcra^tm1Mjo Tg(TcraBDC2.5,TcrbBDC2.5)1Doi induce diabetes at a higher rate than when Ctla4^tm1All/Ctla4⁺ Tg(TcraBDC2.5,TcrbBDC2.5)1Doi splenocytes are used

growth/size/body

enlarged spleen ( J:109887 )

Genotype
MGI:5463746

cx8

• Allelic Composition: H2^g7/H2^g7; Tg(Ins2-Vtcn1)#Xxz/0; Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0
• Genetic Background: involves: C57BL/6 * NOD * SJL

immune system

decreased regulatory T cell number ( J:177612 )

• in the pancreas

decreased interferon-gamma secretion ( J:177612 )

• from CD4+ pancreatic T cells

decreased interleukin-17 secretion ( J:177612 )

• from CD4+ pancreatic T cells

decreased susceptibility to autoimmune diabetes ( J:177612 )

• diabetes disease progression is abrogated compared to in control mice

• however, mice develop insulitis

hematopoietic system

decreased regulatory T cell number ( J:177612 )

• in the pancreas

Genotype
MGI:3625063

cx9

• Allelic Composition: Il4^tm1Cgn/Il4^tm1Cgn; Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0
• Genetic Background: NOD.Cg-Il4^tm1Cgn Tg(TcraBDC2.5,TcrbBDC2.5)1Doi

endocrine/exocrine glands

insulitis ( J:85924 )

• equal degrees of insulitis are detected at 5 weeks in transgenic IL4-deficient NOD mice and control transgenic NOD mice

immune system

insulitis ( J:85924 )

• equal degrees of insulitis are detected at 5 weeks in transgenic IL4-deficient NOD mice and control transgenic NOD mice

decreased susceptibility to autoimmune diabetes ( J:85924 )

• Il4-deficient transgenic NOD mice do not show early or frequent diabetes compared to control transgenic NOD mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:85924

Genotype
MGI:3844820

cx10

• Allelic Composition: Mertk^tm1Gkm/Mertk^tm1Gkm; Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0
• Genetic Background: NOD.Cg-Mertk^tm1Gkm Tg(TcraBDC2.5,TcrbBDC2.5)1Doi

immune system

increased T cell apoptosis ( J:147153 )

• the frequency of double positive T cell apoptosis in thymic lobes is increased compared to in similarly treated heterozygous mice

decreased double-positive T cell number ( J:147153 )

• fetal thymic organ cultures treated with BDC2.5 produce fewer double positive thymocytes than similarly treated heterozygous cells

increased CD8-positive, alpha-beta T cell number ( J:147153 )

• fetal thymic organ cultures treated with BDC2.5 produce more CD8+ single positive thymocytes than similarly treated heterozygous cells

hematopoietic system

increased T cell apoptosis ( J:147153 )

• the frequency of double positive T cell apoptosis in thymic lobes is increased compared to in similarly treated heterozygous mice

decreased double-positive T cell number ( J:147153 )

• fetal thymic organ cultures treated with BDC2.5 produce fewer double positive thymocytes than similarly treated heterozygous cells

increased CD8-positive, alpha-beta T cell number ( J:147153 )

• fetal thymic organ cultures treated with BDC2.5 produce more CD8+ single positive thymocytes than similarly treated heterozygous cells

cellular

increased T cell apoptosis ( J:147153 )

• the frequency of double positive T cell apoptosis in thymic lobes is increased compared to in similarly treated heterozygous mice

Genotype
MGI:3790786

tg11

• Allelic Composition: Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0
• Genetic Background: involves: C57BL/6 * NOD * SJL

digestive/alimentary system

digestive/alimentary phenotype ( J:135214 )

N • peri-islet Schwann cells are intact and surround remaining alpha-cells in contrast to control wild-type NOD mice

immune system

immune system phenotype ( J:135214 )

N

insulitis ( J:137009 )

• treatment with anti-PDCA-1, which depleted plasmocyoid dendritic cells, or 1MT, which neutralize indoleamine 2,3 dioxygenase production, increases the severity of insulitis

decreased dendritic cell number ( J:137009 )

• treatment with anti-PDCA-1 ablates the plasmocytoid dendritic cell population within the pancreatic lymph nodes

endocrine/exocrine glands

insulitis ( J:137009 )

• treatment with anti-PDCA-1, which depleted plasmocyoid dendritic cells, or 1MT, which neutralize indoleamine 2,3 dioxygenase production, increases the severity of insulitis

hematopoietic system

decreased dendritic cell number ( J:137009 )

• treatment with anti-PDCA-1 ablates the plasmocytoid dendritic cell population within the pancreatic lymph nodes

Genotype
MGI:3622335

tg12

• Allelic Composition: Tg(TcraBDC2.5,TcrbBDC2.5)1Doi/0
• Genetic Background: NOD.Cg-Tg(TcraBDC2.5,TcrbBDC2.5)1Doi

immune system

insulitis ( J:52940 )

• insulitis begins abruptly between days 15 and 18 after birth; at 14 days after birth, few activated (CD69+) T cells are detected

increased activated T cell number ( J:52940 )

• in transgenic mice, a large proportion of cells in the pancreatic lymph nodes and pancreatic islets have an activated phenotype (CD4+ Vbeta4+) compared to nontransgenic littermates

decreased susceptibility to autoimmune diabetes ( J:87251 )

• adoptive tranfer of splenocytes from transgenic mice carrying the Tg(TcraBDC2.5)1Doi transgene into knockout recipients led to diabetes after a significant delay compared to diabetes development in wild-type recipients (100% in wild-type by 12 days versus 100% in knockouts by 20 days)

endocrine/exocrine glands

insulitis ( J:52940 )

• insulitis begins abruptly between days 15 and 18 after birth; at 14 days after birth, few activated (CD69+) T cells are detected

hematopoietic system

increased activated T cell number ( J:52940 )

• in transgenic mice, a large proportion of cells in the pancreatic lymph nodes and pancreatic islets have an activated phenotype (CD4+ Vbeta4+) compared to nontransgenic littermates