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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Ctla4tm1Shr
targeted mutation 1, Arlene H Sharpe
MGI:2180668
Summary 8 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
hm1
Ctla4tm1Shr/Ctla4tm1Shr B6.129S4-Ctla4tm1Shr MGI:3838229
hm2
Ctla4tm1Shr/Ctla4tm1Shr C.129S4-Ctla4tm1Shr MGI:3714355
hm3
Ctla4tm1Shr/Ctla4tm1Shr either: (involves: 129S4/SvJae * BALB/c) or (involves: 129S4/SvJae * C57BL/6) MGI:3714292
cx4
Cd28tm1Shr/Cd28tm1Shr
Ctla4tm1Shr/Ctla4tm1Shr
C.129S4-Cd28tm1Shr Ctla4tm1Shr MGI:3721947
cx5
Cd28tm1Shr/Cd28tm1Shr
Ctla4tm1Shr/Ctla4+
C.129S4-Cd28tm1Shr Ctla4tm1Shr MGI:3760760
cx6
Cd80tm1Shr/Cd80tm1Shr
Cd86tm2Shr/Cd86tm2Shr
Ctla4tm1Shr/Ctla4tm1Shr
involves: 129S4/SvJae * BALB/c MGI:3714352
cx7
Ctla4tm1Shr/Ctla4tm1Shr
Tg(DO11.10)10Dlo/0
involves: 129S4/SvJae * BALB/c * C3H * C57BL/6 MGI:3714354
cx8
Ctla4tm1Shr/Ctla4tm1Shr
Rag2tm1Fwa/Rag2tm1Fwa
Tg(DO11.10)10Dlo/0
involves: 129S/Sv * BALB/c * C3H * C57BL/6 MGI:3714326


Genotype
MGI:3838229
hm1
Allelic
Composition
Ctla4tm1Shr/Ctla4tm1Shr
Genetic
Background
B6.129S4-Ctla4tm1Shr
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ctla4tm1Shr mutation (4 available); any Ctla4 mutation (34 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• 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
• wild-type but not Ctla4 null regulatory T cells prevent autoimmune disease when co-transferred with Ctla4 null bone marrow into lymphopenic hosts
• 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
• 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
• wild-type but not Ctla4 null regulatory T cells prevent autoimmune disease when co-transferred with Ctla4 null bone marrow into lymphopenic hosts




Genotype
MGI:3714355
hm2
Allelic
Composition
Ctla4tm1Shr/Ctla4tm1Shr
Genetic
Background
C.129S4-Ctla4tm1Shr
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ctla4tm1Shr mutation (4 available); any Ctla4 mutation (34 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• mice die by 3-4 weeks of age




Genotype
MGI:3714292
hm3
Allelic
Composition
Ctla4tm1Shr/Ctla4tm1Shr
Genetic
Background
either: (involves: 129S4/SvJae * BALB/c) or (involves: 129S4/SvJae * C57BL/6)
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ctla4tm1Shr mutation (4 available); any Ctla4 mutation (34 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• massive splenomegaly observed in 15 to 20-day old mice

cellular
• 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

mortality/aging
• mice die at approximately 3-4 weeks of age

hematopoietic system
• 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
• massive splenomegaly observed in 15 to 20-day old mice
• mutant T cells are larger than wild-type T cells
• 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
• 10-fold decrease in percentage of double-positive CD4+CD8+ T cell in thymus is observed
• relative increase in numbers of CD3+CD4+ and CD3+CD8+ single-positive T cells is seen in thymus
• there is a 5-fold increase in CD4-CD8- double-negative cells in the thymus in 15 to 20-day old mice
• increase in percentage and absolute number of CD3+ cells
• significant decrease in Mel-14+ (naive) T cells in spleen

immune system
• 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
• 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
• some interstitial mononuclear infiltrates in absence of tissue destruction
• 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
• massive splenomegaly observed in 15 to 20-day old mice
• mutant T cells are larger than wild-type T cells
• 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
• 10-fold decrease in percentage of double-positive CD4+CD8+ T cell in thymus is observed
• relative increase in numbers of CD3+CD4+ and CD3+CD8+ single-positive T cells is seen in thymus
• there is a 5-fold increase in CD4-CD8- double-negative cells in the thymus in 15 to 20-day old mice
• increase in percentage and absolute number of CD3+ cells
• significant decrease in Mel-14+ (naive) T cells in spleen
• increase in percentage and absolute number of CD3+ cells at ~15 days of age
• significant decrease in Mel-14+ (naive) T cells in spleen
• massive lymphadenopathy found, with up to 10-fold more lymph node cells in mutants
• 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
• synovitis observed in some mice
• some interstitial mononuclear infiltrates in absence of tissue destruction are seen

endocrine/exocrine glands
• some interstitial mononuclear infiltrates in absence of tissue destruction
• 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

cardiovascular system
• in some mice
• 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

digestive/alimentary system
• some interstitial mononuclear infiltrates in absence of tissue destruction

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

skeleton
• synovitis observed in some mice




Genotype
MGI:3721947
cx4
Allelic
Composition
Cd28tm1Shr/Cd28tm1Shr
Ctla4tm1Shr/Ctla4tm1Shr
Genetic
Background
C.129S4-Cd28tm1Shr Ctla4tm1Shr
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd28tm1Shr mutation (4 available); any Cd28 mutation (38 available)
Ctla4tm1Shr mutation (4 available); any Ctla4 mutation (34 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular
in vitro T cell proliferation is reduced relative to wild-type cells

immune system
in vitro T cell proliferation is reduced relative to wild-type cells
• 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
• upon secondary stimulation in vitro, interferon-gamma levels are increased relative to in wild-type cells
• 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
• allograft survival is increased compared to in wild-type mice but mice eventually reject grafts

hematopoietic system
in vitro T cell proliferation is reduced relative to wild-type cells
• 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
• upon secondary stimulation in vitro, interferon-gamma levels are increased relative to in wild-type cells




Genotype
MGI:3760760
cx5
Allelic
Composition
Cd28tm1Shr/Cd28tm1Shr
Ctla4tm1Shr/Ctla4+
Genetic
Background
C.129S4-Cd28tm1Shr Ctla4tm1Shr
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd28tm1Shr mutation (4 available); any Cd28 mutation (38 available)
Ctla4tm1Shr mutation (4 available); any Ctla4 mutation (34 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
• abnormally high levels of CD5 (a marker of T cell activation) and CD8 expression on T cells

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




Genotype
MGI:3714352
cx6
Allelic
Composition
Cd80tm1Shr/Cd80tm1Shr
Cd86tm2Shr/Cd86tm2Shr
Ctla4tm1Shr/Ctla4tm1Shr
Genetic
Background
involves: 129S4/SvJae * BALB/c
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd80tm1Shr mutation (11 available); any Cd80 mutation (42 available)
Cd86tm2Shr mutation (2 available); any Cd86 mutation (28 available)
Ctla4tm1Shr mutation (4 available); any Ctla4 mutation (34 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular
• during secondary stimulation with anti-CD3 and antigen-presenting cells, CD4+ T cells proliferate more than Ctla4-sufficient, CD80/86 null cells

immune system
• T cells differentiate into Th2 cells upon anti-CD3 stimulus
• during secondary stimulation with anti-CD3 and antigen-presenting cells, CD4+ T cells proliferate more than Ctla4-sufficient, CD80/86 null cells
• 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
• T cells differentiate into Th2 cells upon anti-CD3 stimulus
• during secondary stimulation with anti-CD3 and antigen-presenting cells, CD4+ T cells proliferate more than Ctla4-sufficient, CD80/86 null cells




Genotype
MGI:3714354
cx7
Allelic
Composition
Ctla4tm1Shr/Ctla4tm1Shr
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:
Ctla4tm1Shr mutation (4 available); any Ctla4 mutation (34 available)
Tg(DO11.10)10Dlo mutation (7 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular
• in recall responses, T cells proliferate more than wild-type Tg(DO11.10)10Dlo cells

growth/size/body
• mild splenomegaly observed in 6-8 week-old mice

hematopoietic system
• mild splenomegaly observed in 6-8 week-old mice
• 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
• in recall responses, T cells proliferate more than wild-type Tg(DO11.10)10Dlo cells

immune system
• mild splenomegaly observed in 6-8 week-old mice
• 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
• in recall responses, T cells proliferate more than wild-type Tg(DO11.10)10Dlo cells
• mild lymphadenopathy observed in 6-8 week-old mice




Genotype
MGI:3714326
cx8
Allelic
Composition
Ctla4tm1Shr/Ctla4tm1Shr
Rag2tm1Fwa/Rag2tm1Fwa
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:
Ctla4tm1Shr mutation (4 available); any Ctla4 mutation (34 available)
Rag2tm1Fwa mutation (46 available); any Rag2 mutation (93 available)
Tg(DO11.10)10Dlo mutation (7 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
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
• 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
• 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
• 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





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last database update
01/04/2022
MGI 6.17
The Jackson Laboratory