All Phenotypes Ctla4<tm1Shr> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ctla4^tm1Shr/Ctla4^tm1Shr	B6.129S4-Ctla4^tm1Shr	MGI:3838229
hm2	Ctla4^tm1Shr/Ctla4^tm1Shr	C.129S4-Ctla4^tm1Shr	MGI:3714355
hm3	Ctla4^tm1Shr/Ctla4^tm1Shr	either: (involves: 129S4/SvJae * BALB/c) or (involves: 129S4/SvJae * C57BL/6)	MGI:3714292
cx4	Cd28^tm1Shr/Cd28^tm1Shr Ctla4^tm1Shr/Ctla4^tm1Shr	C.129S4-Cd28^tm1Shr Ctla4^tm1Shr	MGI:3721947
cx5	Cd28^tm1Shr/Cd28^tm1Shr Ctla4^tm1Shr/Ctla4⁺	C.129S4-Cd28^tm1Shr Ctla4^tm1Shr	MGI:3760760
cx6	Cd80^tm1Shr/Cd80^tm1Shr Cd86^tm2Shr/Cd86^tm2Shr Ctla4^tm1Shr/Ctla4^tm1Shr	involves: 129S4/SvJae * BALB/c	MGI:3714352
cx7	Ctla4^tm1Shr/Ctla4^tm1Shr Tg(DO11.10)10Dlo/0	involves: 129S4/SvJae * BALB/c * C3H * C57BL/6	MGI:3714354
cx8	Ctla4^tm1Shr/Ctla4^tm1Shr Rag2^tm1Fwa/Rag2^tm1Fwa Tg(DO11.10)10Dlo/0	involves: 129S/Sv * BALB/c * C3H * C57BL/6	MGI:3714326

Allelic Composition	Ctla4^tm1Shr/Ctla4^tm1Shr
Genetic Background	B6.129S4-Ctla4^tm1Shr

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ctla4^tm1Shr mutation (4 available); any Ctla4 mutation (54 available)

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

immune system

abnormal T cell physiology ( J:146644 )

• mutant bone marrow transferred to lymphopenic hosts generates auto-reactive T cells that propagate a multi-organ inflammatory disease

• the same pathological response occurs when chimeric mice are created from Ctla4 null and Rag1 null blastocytes

• mixing of WT, Tcrd null, CD4 null, CD8a null or B7 null bone marrow with Ctla4 null bone marrow prevents autoreactive Ctla4 null T cells from propagating disease

• mixing of Tcrb null or CD28 null bone marrow with Ctla4 null bone marrow fails to prevent disease

abnormal regulatory T cell physiology ( J:146644 )

• wild-type but not Ctla4 null regulatory T cells prevent autoimmune disease when co-transferred with Ctla4 null bone marrow into lymphopenic hosts

autoimmune response ( J:146644 )

• mutant bone marrow transferred to lymphopenic hosts generates auto-reactive T cells that propagate a multi-organ inflammatory disease

• the same pathological response occurs when chimeric mice are created from Ctla4 null and Rag1 null blastocytes

hematopoietic system

abnormal T cell physiology ( J:146644 )

• mutant bone marrow transferred to lymphopenic hosts generates auto-reactive T cells that propagate a multi-organ inflammatory disease

• the same pathological response occurs when chimeric mice are created from Ctla4 null and Rag1 null blastocytes

• mixing of WT, Tcrd null, CD4 null, CD8a null or B7 null bone marrow with Ctla4 null bone marrow prevents autoreactive Ctla4 null T cells from propagating disease

• mixing of Tcrb null or CD28 null bone marrow with Ctla4 null bone marrow fails to prevent disease

abnormal regulatory T cell physiology ( J:146644 )

• wild-type but not Ctla4 null regulatory T cells prevent autoimmune disease when co-transferred with Ctla4 null bone marrow into lymphopenic hosts

Allelic Composition	Ctla4^tm1Shr/Ctla4^tm1Shr
Genetic Background	C.129S4-Ctla4^tm1Shr

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ctla4^tm1Shr mutation (4 available); any Ctla4 mutation (54 available)

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

mortality/aging

premature death ( J:57090 )

• mice die by 3-4 weeks of age

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

mortality/aging

premature death ( J:30393 )

• mice die at approximately 3-4 weeks of age

hematopoietic system

increased T cell proliferation ( J:30393 )

• vigorous spontaneous proliferation of lymph node cells is seen in culture, with moderate proliferation of spleen cells in culture, compared to no spontaneous proliferation of cultured wild-type cells; ~80% of cells are CD4+CD8- single-positive cells and 20% are CD4-CD8+ single-positives after 6 days in culture

enlarged spleen ( J:30393 )

• massive splenomegaly observed in 15 to 20-day old mice

abnormal T cell morphology ( J:30393 )

• mutant T cells are larger than wild-type T cells

abnormal T cell differentiation ( J:30393 )

• increase is seen in percentage and expression levels of activation markers CD69, CD25, and CD44 on T cells in spleen and lymph nodes

• mutant T cells are larger than wild-type T cells

decreased double-positive T cell number ( J:30393 )

• 10-fold decrease in percentage of double-positive CD4+CD8+ T cell in thymus is observed

increased T cell number ( J:30393 )

• relative increase in numbers of CD3+CD4+ and CD3+CD8+ single-positive T cells is seen in thymus

increased double-negative T cell number ( J:30393 )

• there is a 5-fold increase in CD4-CD8- double-negative cells in the thymus in 15 to 20-day old mice

abnormal splenic cell ratio ( J:30393 )

• increase in percentage and absolute number of CD3+ cells

• significant decrease in Mel-14+ (naive) T cells in spleen

immune system

myocarditis ( J:30393 )

• destructive myocarditis is seen with massive interstitial infiltrates consisting of abundant CD3+ cells, CD4+ and CD8+ cells, numerous macrophages, and occasional B220+ B cells, as well as neutrophils in mice at ~15 days of age

increased T cell proliferation ( J:30393 )

salivary gland inflammation ( J:30393 )

• some interstitial mononuclear infiltrates in absence of tissue destruction

pancreas inflammation ( J:30393 )

• severe pancreatitis is seen with intense mononuclear infiltrate with destruction of islets and glandular elements; infiltrates consist of abundant CD3+ cells, CD4+ and CD8+ cells, numerous macrophages, and occasional B220+ B cells at ~15 days of age

enlarged spleen ( J:30393 )

• massive splenomegaly observed in 15 to 20-day old mice

abnormal T cell morphology ( J:30393 )

• mutant T cells are larger than wild-type T cells

abnormal T cell differentiation ( J:30393 )

• increase is seen in percentage and expression levels of activation markers CD69, CD25, and CD44 on T cells in spleen and lymph nodes

• mutant T cells are larger than wild-type T cells

decreased double-positive T cell number ( J:30393 )

• 10-fold decrease in percentage of double-positive CD4+CD8+ T cell in thymus is observed

increased T cell number ( J:30393 )

• relative increase in numbers of CD3+CD4+ and CD3+CD8+ single-positive T cells is seen in thymus

increased double-negative T cell number ( J:30393 )

• there is a 5-fold increase in CD4-CD8- double-negative cells in the thymus in 15 to 20-day old mice

abnormal splenic cell ratio ( J:30393 )

• increase in percentage and absolute number of CD3+ cells

• significant decrease in Mel-14+ (naive) T cells in spleen

abnormal lymph node cell ratio ( J:30393 )

• increase in percentage and absolute number of CD3+ cells at ~15 days of age

• significant decrease in Mel-14+ (naive) T cells in spleen

enlarged lymph nodes ( J:30393 )

• massive lymphadenopathy found, with up to 10-fold more lymph node cells in mutants

abnormal cytokine secretion ( J:30393 )

• analysis of supernatants from anti-CD3-stimulated lymph node and spleen cells show increased amounts of interferon gamma (Ifng), interleukin-4 (Il-4), and granulocyte-macrophage colony-stimulating factor compared to cells from wild-type mice

joint inflammation ( J:30393 )

• synovitis observed in some mice

lung inflammation ( J:30393 )

• some interstitial mononuclear infiltrates in absence of tissue destruction are seen

endocrine/exocrine glands

salivary gland inflammation ( J:30393 )

• some interstitial mononuclear infiltrates in absence of tissue destruction

pancreas inflammation ( J:30393 )

cardiovascular system

vascular inflammation ( J:30393 )

• in some mice

myocarditis ( J:30393 )

digestive/alimentary system

salivary gland inflammation ( J:30393 )

• some interstitial mononuclear infiltrates in absence of tissue destruction

respiratory system

lung inflammation ( J:30393 )

• some interstitial mononuclear infiltrates in absence of tissue destruction are seen

skeleton

joint inflammation ( J:30393 )

• synovitis observed in some mice

growth/size/body

enlarged spleen ( J:30393 )

• massive splenomegaly observed in 15 to 20-day old mice

cellular

increased T cell proliferation ( J:30393 )

Allelic Composition	Cd28^tm1Shr/Cd28^tm1Shr Ctla4^tm1Shr/Ctla4^tm1Shr
Genetic Background	C.129S4-Cd28^tm1Shr Ctla4^tm1Shr

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd28^tm1Shr mutation (4 available); any Cd28 mutation (52 available)
Ctla4^tm1Shr mutation (4 available); any Ctla4 mutation (54 available)

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

immune system

decreased T cell proliferation ( J:68642 )

• in vitro T cell proliferation is reduced relative to wild-type cells

decreased CD4-positive, alpha-beta T cell number ( J:68642 )

• the number of CD4+ CD69+ T cells is reduced by 50% compared to in wild-type mice

• however, T and B cell development is normal

abnormal interferon level ( J:68642 )

• upon secondary stimulation in vitro, interferon-gamma levels are increased relative to in wild-type cells

abnormal interleukin secretion ( J:68642 )

• upon primary stimulation in vitro, IL-2 production is decreased by 50% relative to in wild-type cells

• upon secondary stimulation in vitro, IL-4 and IL-10 production is decreased relative to in wild-type cells

increased length of allograft survival ( J:68642 )

• allograft survival is increased compared to in wild-type mice but mice eventually reject grafts

hematopoietic system

decreased T cell proliferation ( J:68642 )

• in vitro T cell proliferation is reduced relative to wild-type cells

decreased CD4-positive, alpha-beta T cell number ( J:68642 )

• the number of CD4+ CD69+ T cells is reduced by 50% compared to in wild-type mice

• however, T and B cell development is normal

homeostasis/metabolism

abnormal interferon level ( J:68642 )

• upon secondary stimulation in vitro, interferon-gamma levels are increased relative to in wild-type cells

cellular

decreased T cell proliferation ( J:68642 )

• in vitro T cell proliferation is reduced relative to wild-type cells

Allelic Composition	Cd28^tm1Shr/Cd28^tm1Shr Ctla4^tm1Shr/Ctla4⁺
Genetic Background	C.129S4-Cd28^tm1Shr Ctla4^tm1Shr

Find Mice

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

hematopoietic system

abnormal CD8-positive, alpha beta T cell morphology ( J:125259 )

• abnormally high levels of CD5 (a marker of T cell activation) and CD8 expression on T cells

immune system

abnormal CD8-positive, alpha beta T cell morphology ( J:125259 )

• abnormally high levels of CD5 (a marker of T cell activation) and CD8 expression on T cells

increased susceptibility to autoimmune disorder ( J:125259 )

Allelic Composition	Cd80^tm1Shr/Cd80^tm1Shr Cd86^tm2Shr/Cd86^tm2Shr Ctla4^tm1Shr/Ctla4^tm1Shr
Genetic Background	involves: 129S4/SvJae * BALB/c

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd80^tm1Shr mutation (12 available); any Cd80 mutation (44 available)
Cd86^tm2Shr mutation (3 available); any Cd86 mutation (39 available)
Ctla4^tm1Shr mutation (4 available); any Ctla4 mutation (54 available)

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

immune system

abnormal T cell physiology ( J:57090 )

• T cells differentiate into Th2 cells upon anti-CD3 stimulus

increased T cell proliferation ( J:57090 )

• during secondary stimulation with anti-CD3 and antigen-presenting cells, CD4+ T cells proliferate more than Ctla4-sufficient, CD80/86 null cells

abnormal cytokine secretion ( J:57090 )

• cells produce Il-4 even during primary stimulation with anti-CD3 and APCs, whereas Ctla4-sufficient mice do not, and on secondary stimulation, cells produce more Il-4 and less interferon gamma than Ctla4-sufficient cells

• upon anti-CD28 stimulation in vivo, cells produce Il-4 but wild-type cells do not; mice show less interferon gamma production after anti-CD28 treatment than wild-type mice

hematopoietic system

abnormal T cell physiology ( J:57090 )

• T cells differentiate into Th2 cells upon anti-CD3 stimulus

increased T cell proliferation ( J:57090 )

• during secondary stimulation with anti-CD3 and antigen-presenting cells, CD4+ T cells proliferate more than Ctla4-sufficient, CD80/86 null cells

cellular

increased T cell proliferation ( J:57090 )

• during secondary stimulation with anti-CD3 and antigen-presenting cells, CD4+ T cells proliferate more than Ctla4-sufficient, CD80/86 null cells

Allelic Composition	Ctla4^tm1Shr/Ctla4^tm1Shr Tg(DO11.10)10Dlo/0
Genetic Background	involves: 129S4/SvJae * BALB/c * C3H * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ctla4^tm1Shr mutation (4 available); any Ctla4 mutation (54 available)
Tg(DO11.10)10Dlo mutation (7 available)

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

hematopoietic system

enlarged spleen ( J:57090 )

• mild splenomegaly observed in 6-8 week-old mice

abnormal T cell physiology ( J:57090 )

• 3 to 4 days after priming with ovalbumin peptide and antigen-presenting cells, T cells produce Il-4, whereas Ctla4-sufficient, Tg(DO11.10)10Dlo cells do not

• T cells produce Th2 cytokines (Il-4, Il-5, and Il-10) upon restimulation with antigen and APCs, whereas Tg(DO11.10)10Dlo cells produce the Th1 cytokine interferon gamma; Th2 bias is seen over a range of peptide concentration during primary stimulation

increased T cell proliferation ( J:57090 )

• in recall responses, T cells proliferate more than wild-type Tg(DO11.10)10Dlo cells

immune system

enlarged spleen ( J:57090 )

• mild splenomegaly observed in 6-8 week-old mice

abnormal T cell physiology ( J:57090 )

• 3 to 4 days after priming with ovalbumin peptide and antigen-presenting cells, T cells produce Il-4, whereas Ctla4-sufficient, Tg(DO11.10)10Dlo cells do not

increased T cell proliferation ( J:57090 )

• in recall responses, T cells proliferate more than wild-type Tg(DO11.10)10Dlo cells

enlarged lymph nodes ( J:57090 )

• mild lymphadenopathy observed in 6-8 week-old mice

growth/size/body

enlarged spleen ( J:57090 )

• mild splenomegaly observed in 6-8 week-old mice

cellular

increased T cell proliferation ( J:57090 )

• in recall responses, T cells proliferate more than wild-type Tg(DO11.10)10Dlo cells

Allelic Composition	Ctla4^tm1Shr/Ctla4^tm1Shr Rag2^tm1Fwa/Rag2^tm1Fwa Tg(DO11.10)10Dlo/0
Genetic Background	involves: 129S/Sv * BALB/c * C3H * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ctla4^tm1Shr mutation (4 available); any Ctla4 mutation (54 available)
Rag2^tm1Fwa mutation (45 available); any Rag2 mutation (119 available)
Tg(DO11.10)10Dlo mutation (7 available)

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

immune system

immune system phenotype ( J:110446 )

N	• mice show no signs of T cell activation, lymphadenopathy, or splenomegaly over 32 weeks; T cells are naive, with no expression of activation markers • primary response to antigen stimulation in vitro is similar to Rag1-null, Tg(DO11.10)10Dlo T cells

abnormal T cell physiology ( J:110446 )

• during secondary response to low-dose antigen stimulation in vitro, T cells show 2.2-3 fold higher proliferation compared to Rag2-null, Tg(Do11.10)10Dlo mice

• transferred T cells are resistant to tolerance induction in vivo in hosts after a tolerizing dose of ovalbumin peptide; in vivo expansion of T cells 4 and 7 days after treatment is 2.2- and 1.4-fold greater than Rag2-null, transgenic mice

• T cells given a tolerogenic stimulus proliferate and secrete Il-2 robustly upon restimulation in contrast to poor response in Rag2-null, Tg(DO11.10)10Dlo mice

• T cells given a tolerogenic stimulus do not exhibit a blockade after entering G1 phase of cell cycle, and readily enter S phase, while Ctla4-sufficient mutant cells do not progress past G1

abnormal cytokine secretion ( J:110446 )

• during secondary response, on days 2 and 3, T cells show increased production of interferon gamma and Il-4 than transgenic, Rag2-null mice

hematopoietic system

abnormal T cell physiology ( J:110446 )

• during secondary response to low-dose antigen stimulation in vitro, T cells show 2.2-3 fold higher proliferation compared to Rag2-null, Tg(Do11.10)10Dlo mice

• T cells given a tolerogenic stimulus proliferate and secrete Il-2 robustly upon restimulation in contrast to poor response in Rag2-null, Tg(DO11.10)10Dlo mice

• T cells given a tolerogenic stimulus do not exhibit a blockade after entering G1 phase of cell cycle, and readily enter S phase, while Ctla4-sufficient mutant cells do not progress past G1

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