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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Tg(CD2-icre)4Kio
transgene insertion 4, Dimitris Kioussis
MGI:2449947
Summary 19 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
cn1
Gimap1tm1.1Gwb/Gimap1tm1.1Gwb
Tg(CD2-icre)4Kio/0
involves: 129 * C57BL/6 * C57BL/10 * CBA/Ca MGI:4459839
cn2
Nampttm1Oleo/Nampttm1Oleo
Tg(CD2-icre)4Kio/0
involves: 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/10 * CBA/Ca MGI:3818632
cn3
Septin7tm1Mgl/Septin7tm1Mgl
Tg(CD2-icre)4Kio/0
involves: 129P2/OlaHsd * C3H * C57BL/6 * C57BL/10 * CBA/Ca MGI:5660277
cn4
Noc2ltm1.1Arte/Noc2ltm1.1Arte
Trp53tm1Brn/Trp53tm1Brn
Tg(CD2-icre)4Kio/0
involves: 129P2/OlaHsd * C57BL/6 * C57BL/10 * CBA/Ca MGI:5662110
cn5
Bcl2l11tm1.1Ast/Bcl2l11+
Ptentm1Hwu/Pten+
Tg(CD2-icre)4Kio/0
involves: 129S1/Sv * 129S4/SvJae * C57BL/10 * CBA/Ca MGI:3783573
cn6
Rettm6.1Vpa/Rettm6.2Vpa
Tg(CD2-icre)4Kio/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/10 * CBA/Ca MGI:5489749
cn7
Etv6tm1(RUNX1)Haho/Etv6+
Tg(CD2-icre)4Kio/0
involves: 129S1/Sv * C57BL/6 * C57BL/10 * CBA/Ca MGI:4356081
cn8
Gmnntm1.1Kio/Gmnntm1.2Kio
Tg(CD2-icre)4Kio/0
involves: 129S4/SvJae * C57BL/10 * CBA/Ca MGI:4456379
cn9
Rr7tm3.1Kio/Rr7+
Tg(CD2-icre)4Kio/0
involves: 129S4/SvJae * C57BL/6 * C57BL/10 * CBA/Ca MGI:5305075
cn10
Pkn3tm1.1Mrl/Pkn3tm1.1Mrl
Ptentm1Hwu/Ptentm1Hwu
Tg(CD2-icre)4Kio/0
involves: 129S4/SvJae * C57BL/6 * C57BL/10 * CBA/Ca MGI:5688869
cn11
Ptentm1Hwu/Ptentm1Hwu
Tg(CD2-icre)4Kio/0
involves: 129S4/SvJae * C57BL/6 * C57BL/10 * CBA/Ca MGI:5688871
cn12
Syktm1.1Nns/Syktm1.1Nns
Tg(CD2-icre)4Kio/0
involves: C57BL/10 * CBA/Ca MGI:5314237
cn13
Ikzf1tm3Kge/Ikzf1tm3Kge
Tg(CD2-icre)4Kio/?
involves: C57BL/10 * CBA/Ca MGI:5698879
cn14
Gt(ROSA)26Sortm3(CAG-MIR17-92,-EGFP)Rsky/Gt(ROSA)26Sortm3(CAG-MIR17-92,-EGFP)Rsky
Tg(CD2-icre)4Kio/0
involves: C57BL/6 * C57BL/10 * CBA/Ca MGI:3783575
cn15
Gt(ROSA)26Sortm3(CAG-MIR17-92,-EGFP)Rsky/Gt(ROSA)26Sor+
Tg(CD2-icre)4Kio/0
involves: C57BL/6 * C57BL/10 * CBA/Ca MGI:3783574
cn16
Mir146tm1.1Lfl/Mir146tm1.1Lfl
Tg(CD2-icre)4Kio/0
involves: C57BL/6 * C57BL/10 * CBA/Ca MGI:6360065
cn17
Gimap6tm1.1Gwb/Gimap6tm1.1Gwb
Tg(CD2-icre)4Kio/0
involves: C57BL/6 * C57BL/10 * CBA/Ca MGI:6160464
cn18
Noc2ltm1.1Arte/Noc2ltm1.1Arte
Tg(CD2-icre)4Kio/0
involves: C57BL/6 * C57BL/10 * CBA/Ca MGI:5662109
cn19
Zfp36l1tm1.1Tnr/Zfp36l1tm1.1Tnr
Zfp36l2tm1.1Tnr/Zfp36l2tm1.1Tnr
Tg(CD2-icre)4Kio/0
involves: C57BL/6 * C57BL/10 * CBA/Ca * SJL MGI:4819157


Genotype
MGI:4459839
cn1
Allelic
Composition
Gimap1tm1.1Gwb/Gimap1tm1.1Gwb
Tg(CD2-icre)4Kio/0
Genetic
Background
involves: 129 * C57BL/6 * C57BL/10 * CBA/Ca
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gimap1tm1.1Gwb mutation (0 available); any Gimap1 mutation (6 available)
Tg(CD2-icre)4Kio mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
• the overall spleenic cellularity is reduced by approximately 40%
• the lymph node cellualrity is severely reduced
• in lymph nodes
• in peritoneum
• in peritoneum
• in peritoneum
• in peritoneum and blood
• in spleen and lymph node and the CD4 single positive subset in the thymus
• in spleen and lymph node and the CD8 single positive subset in the thymus
• decreased thymocyte survival in culture
• a trend towards decreased thymocyte survival in culture

immune system
• the overall spleenic cellularity is reduced by approximately 40%
• the lymph node cellualrity is severely reduced
• in lymph nodes
• in peritoneum
• in peritoneum
• in peritoneum
• in peritoneum and blood
• in spleen and lymph node and the CD4 single positive subset in the thymus
• in spleen and lymph node and the CD8 single positive subset in the thymus
• decreased thymocyte survival in culture
• a trend towards decreased thymocyte survival in culture

endocrine/exocrine glands




Genotype
MGI:3818632
cn2
Allelic
Composition
Nampttm1Oleo/Nampttm1Oleo
Tg(CD2-icre)4Kio/0
Genetic
Background
involves: 129P2/OlaHsd * 129S4/SvJaeSor * C57BL/10 * CBA/Ca
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Nampttm1Oleo mutation (0 available); any Nampt mutation (58 available)
Tg(CD2-icre)4Kio mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• thymic cell numbers are decreased 95% compared to in wild-type mice
• mice exhibit a near complete lack of peripheral B cells
• mice exhibit a near complete lack of peripheral T cells
• mice exhibit a near complete absence of double negative T cells compared to in wild-type mice

hematopoietic system
• thymic cell numbers are decreased 95% compared to in wild-type mice
• mice exhibit a near complete lack of peripheral B cells
• mice exhibit a near complete lack of peripheral T cells
• mice exhibit a near complete absence of double negative T cells compared to in wild-type mice

endocrine/exocrine glands
• thymic cell numbers are decreased 95% compared to in wild-type mice




Genotype
MGI:5660277
cn3
Allelic
Composition
Septin7tm1Mgl/Septin7tm1Mgl
Tg(CD2-icre)4Kio/0
Genetic
Background
involves: 129P2/OlaHsd * C3H * C57BL/6 * C57BL/10 * CBA/Ca
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Septin7tm1Mgl mutation (0 available); any Septin7 mutation (25 available)
Tg(CD2-icre)4Kio mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
N
• mice exhibit normal numbers of peripheral blood cells
• myeloid cells and lymphoid cells exhibit normal cytokinesis




Genotype
MGI:5662110
cn4
Allelic
Composition
Noc2ltm1.1Arte/Noc2ltm1.1Arte
Trp53tm1Brn/Trp53tm1Brn
Tg(CD2-icre)4Kio/0
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6 * C57BL/10 * CBA/Ca
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Noc2ltm1.1Arte mutation (0 available); any Noc2l mutation (0 available)
Tg(CD2-icre)4Kio mutation (4 available)
Trp53tm1Brn mutation (13 available); any Trp53 mutation (152 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
N
• rescue of the CD4+CD8+ double positive thymocyte developmental defect
• significant increase in the number of single positive thymocytes in comparison to mutant mice wild-type for Trp53
• significant recovery of DN3L cells close to levels in control mice
• significant increase in the number of late pro-B cells in comparison to mutant mice wild-type for Trp53
• numbers of pre-B (IgM+B220+CD19+CD43-) are not increased by the absence of Trp53 expression

immune system
• numbers of pre-B (IgM+B220+CD19+CD43-) are not increased by the absence of Trp53 expression




Genotype
MGI:3783573
cn5
Allelic
Composition
Bcl2l11tm1.1Ast/Bcl2l11+
Ptentm1Hwu/Pten+
Tg(CD2-icre)4Kio/0
Genetic
Background
involves: 129S1/Sv * 129S4/SvJae * C57BL/10 * CBA/Ca
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Bcl2l11tm1.1Ast mutation (4 available); any Bcl2l11 mutation (15 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (38 available)
Tg(CD2-icre)4Kio mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• at 20 to 28 weeks of age, mice exhibit increased germinal center B cell number compared to controls but not as much as in Gt(ROSA)26Sortm3Rsky/Gt(ROSA)26Sortm3Rsky/ Tg(CD2-cre)1Kio mice
• at 20 to 28 weeks of age, mice accumulate more antigen-experienced T cells than in control mice but not as much as in Gt(ROSA)26Sortm3Rsky/Gt(ROSA)26Sortm3Rsky/ Tg(CD2-cre)1Kio mice

hematopoietic system
• at 20 to 28 weeks of age, mice exhibit increased germinal center B cell number compared to controls but not as much as in Gt(ROSA)26Sortm3Rsky/Gt(ROSA)26Sortm3Rsky/ Tg(CD2-cre)1Kio mice
• at 20 to 28 weeks of age, mice accumulate more antigen-experienced T cells than in control mice but not as much as in Gt(ROSA)26Sortm3Rsky/Gt(ROSA)26Sortm3Rsky/ Tg(CD2-cre)1Kio mice




Genotype
MGI:5489749
cn6
Allelic
Composition
Rettm6.1Vpa/Rettm6.2Vpa
Tg(CD2-icre)4Kio/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/10 * CBA/Ca
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rettm6.1Vpa mutation (0 available); any Ret mutation (35 available)
Rettm6.2Vpa mutation (0 available); any Ret mutation (35 available)
Tg(CD2-icre)4Kio mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
N
• bone marrow cells are capable of normal

immune system
N
• mice exhibit normal fetal and adult T cell development




Genotype
MGI:4356081
cn7
Allelic
Composition
Etv6tm1(RUNX1)Haho/Etv6+
Tg(CD2-icre)4Kio/0
Genetic
Background
involves: 129S1/Sv * C57BL/6 * C57BL/10 * CBA/Ca
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Etv6tm1(RUNX1)Haho mutation (1 available); any Etv6 mutation (123 available)
Tg(CD2-icre)4Kio mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
N
• T and B cell development is normal




Genotype
MGI:4456379
cn8
Allelic
Composition
Gmnntm1.1Kio/Gmnntm1.2Kio
Tg(CD2-icre)4Kio/0
Genetic
Background
involves: 129S4/SvJae * C57BL/10 * CBA/Ca
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gmnntm1.1Kio mutation (0 available); any Gmnn mutation (5 available)
Gmnntm1.2Kio mutation (0 available); any Gmnn mutation (5 available)
Tg(CD2-icre)4Kio mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular
• in response to mitogenic stimulation (anti-CD3 plus anti-CD28, or PDBU and ionomycin or Con A), T cells exhibit decreased proliferation compared with similarly treated control cells
• anti-CD3 and anti-CD28-treated T cells exhibit an increase in percentage of cells at the G2/M phase and accumulate in G2 phase compared with similarly treated control cells
• T cells fail to exhibit spontaneous proliferation in a T cell depleted mouse with reduced CD8 T cells compared with control cells
• however, T cells exhibit normal apoptosis and entry into S phase

immune system
• in response to mitogenic stimulation (anti-CD3 plus anti-CD28, or PDBU and ionomycin or Con A), T cells exhibit decreased proliferation compared with similarly treated control cells
• anti-CD3 and anti-CD28-treated T cells exhibit an increase in percentage of cells at the G2/M phase and accumulate in G2 phase compared with similarly treated control cells
• T cells fail to exhibit spontaneous proliferation in a T cell depleted mouse with reduced CD8 T cells compared with control cells
• however, T cells exhibit normal apoptosis and entry into S phase
• mice exhibit a reduction of CD4+, CD4+CD62L-, and CD4+CD44hi cells compared with control mice
• mice exhibit a reduction of CD8+ and CD8+CD62L- cells compared with control mice

hematopoietic system
• in response to mitogenic stimulation (anti-CD3 plus anti-CD28, or PDBU and ionomycin or Con A), T cells exhibit decreased proliferation compared with similarly treated control cells
• anti-CD3 and anti-CD28-treated T cells exhibit an increase in percentage of cells at the G2/M phase and accumulate in G2 phase compared with similarly treated control cells
• T cells fail to exhibit spontaneous proliferation in a T cell depleted mouse with reduced CD8 T cells compared with control cells
• however, T cells exhibit normal apoptosis and entry into S phase
• mice exhibit a reduction of CD4+, CD4+CD62L-, and CD4+CD44hi cells compared with control mice
• mice exhibit a reduction of CD8+ and CD8+CD62L- cells compared with control mice

endocrine/exocrine glands




Genotype
MGI:5305075
cn9
Allelic
Composition
Rr7tm3.1Kio/Rr7+
Tg(CD2-icre)4Kio/0
Genetic
Background
involves: 129S4/SvJae * C57BL/6 * C57BL/10 * CBA/Ca
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rr7tm3.1Kio mutation (0 available); any Rr7 mutation (0 available)
Tg(CD2-icre)4Kio mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
N
• mice exhibit normal expression of Cd8a and Cd8b




Genotype
MGI:5688869
cn10
Allelic
Composition
Pkn3tm1.1Mrl/Pkn3tm1.1Mrl
Ptentm1Hwu/Ptentm1Hwu
Tg(CD2-icre)4Kio/0
Genetic
Background
involves: 129S4/SvJae * C57BL/6 * C57BL/10 * CBA/Ca
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pkn3tm1.1Mrl mutation (0 available); any Pkn3 mutation (30 available)
Ptentm1Hwu mutation (3 available); any Pten mutation (38 available)
Tg(CD2-icre)4Kio mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
N
• thymus weight is similar to controls at 6-8 weeks of age unlike in mutant mice wild-type for Pkn3




Genotype
MGI:5688871
cn11
Allelic
Composition
Ptentm1Hwu/Ptentm1Hwu
Tg(CD2-icre)4Kio/0
Genetic
Background
involves: 129S4/SvJae * C57BL/6 * C57BL/10 * CBA/Ca
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptentm1Hwu mutation (3 available); any Pten mutation (38 available)
Tg(CD2-icre)4Kio mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
• at 6-8 weeks of age

endocrine/exocrine glands
• at 6-8 weeks of age

immune system
• at 6-8 weeks of age




Genotype
MGI:5314237
cn12
Allelic
Composition
Syktm1.1Nns/Syktm1.1Nns
Tg(CD2-icre)4Kio/0
Genetic
Background
involves: C57BL/10 * CBA/Ca
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Syktm1.1Nns mutation (0 available); any Syk mutation (28 available)
Tg(CD2-icre)4Kio mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
N
• mice exhibit normal perinatal survival

immune system
N
• mice exhibit normal lymphatic vessels

homeostasis/metabolism
N
• mice do not exhibit edema




Genotype
MGI:5698879
cn13
Allelic
Composition
Ikzf1tm3Kge/Ikzf1tm3Kge
Tg(CD2-icre)4Kio/?
Genetic
Background
involves: C57BL/10 * CBA/Ca
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ikzf1tm3Kge mutation (0 available); any Ikzf1 mutation (5 available)
Tg(CD2-icre)4Kio mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• rapid development of T lymphoid neoplasms

hematopoietic system
• large pre-B cells fail to differentiate further in culture
• grow better than controls on a bone marrow stroma, 2-10 fold more cells in the cell cycle
• greater colony forming potential on bone marrow stroma than control cells
• pre-B cells unable to migrate in response to CXCL12

neoplasm
• rapid development of T lymphoid neoplasms

immune system
• large pre-B cells fail to differentiate further in culture
• grow better than controls on a bone marrow stroma, 2-10 fold more cells in the cell cycle
• greater colony forming potential on bone marrow stroma than control cells
• pre-B cells unable to migrate in response to CXCL12




Genotype
MGI:3783575
cn14
Allelic
Composition
Gt(ROSA)26Sortm3(CAG-MIR17-92,-EGFP)Rsky/Gt(ROSA)26Sortm3(CAG-MIR17-92,-EGFP)Rsky
Tg(CD2-icre)4Kio/0
Genetic
Background
involves: C57BL/6 * C57BL/10 * CBA/Ca
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm3(CAG-MIR17-92,-EGFP)Rsky mutation (1 available); any Gt(ROSA)26Sor mutation (510 available)
Tg(CD2-icre)4Kio mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
cellular
• B-2 cell proliferation is enhanced following activation with anti-IgM or lipopolysaccharides unlike in wild-type cells

mortality/aging
• all mice die by 55 weeks of age

immune system
N
• despite increased immunoglobulin, cytokine levels in the blood are normal
• prior to 14 weeks of age, mice exhibit a 2-fold higher percentage of thymocytes at the double negative stage compared to in wild-type mice
• however, the total number of thymocytes is unchanged
• at 5 weeks of age
• in the spleen and peripheral lymph nodes
• mice exhibit more CD19+B220loCD5+CD43+CD23- B-1a cells in the spleen and peritoneal cavity compared to in wild-type mice
• spleen and lymph node B cells exhibit increased cell size compared to in wild-type mice
• CD4+ T cells exhibit increased proliferation and survival following stimulation with CD3 alone unlike wild-type cells
• spleens and lymph nodes are enlarged up to 30-fold in terms of weight and cell number compared to in wild-type mice
• spleens and lymph nodes are enlarged up to 30-fold in terms of weight and cell number compared to in wild-type mice
• the spleen marginal zone is disrupted unlike in wild-type mice
• spleens and lymph nodes are enlarged up to 30-fold in terms of weight and cell number compared to in wild-type mice
• spleens and lymph nodes are enlarged up to 30-fold in terms of weight and cell number compared to in wild-type mice
• mice exhibit massive infiltration of lymphocytes into the salivary glands and lungs with some infiltration of the kidneys unlike in wild-type mice
• B cells are more resistance than in wild-type mice to Fas-mediated cell death following activation
• activated B cells exhibit enhanced proliferation and survival compared to wild-type cells
• B-2 cell proliferation is enhanced following activation with anti-IgM or lipopolysaccharides unlike in wild-type cells
• 4- to 6-fold at 8 to 12 weeks of age
• 4- to 6-fold at 8 to 12 weeks of age
• 4- to 6-fold at 8 to 12 weeks of age
• 4- to 6-fold at 8 to 12 weeks of age
• more CD4+ T cells produce IFN-gamma and IL-10 but not IL-4 or TNF than wild-type cells
• CD4+T cells from older mice produce more IFN-gamma and IL-10 than CD4+ T cells from younger mice
• activated T cells exhibit enhanced proliferation and survival compared to wild-type cells

renal/urinary system
• a subset of mice show marked accumulation of IgG and the C3d component of complement in the mesangium and segmentally in the periphery of glomeruli
• mice exhibit mesangial expansion unlike in wild-type mice
• mice exhibit enlarged renal glomeruli with hypercellularity and mesangial expansion unlike in wild-type mice
• in some mice

homeostasis/metabolism

hematopoietic system
• prior to 14 weeks of age, mice exhibit a 2-fold higher percentage of thymocytes at the double negative stage compared to in wild-type mice
• however, the total number of thymocytes is unchanged
• at 5 weeks of age
• in the spleen and peripheral lymph nodes
• mice exhibit more CD19+B220loCD5+CD43+CD23- B-1a cells in the spleen and peritoneal cavity compared to in wild-type mice
• spleen and lymph node B cells exhibit increased cell size compared to in wild-type mice
• CD4+ T cells exhibit increased proliferation and survival following stimulation with CD3 alone unlike wild-type cells
• spleens and lymph nodes are enlarged up to 30-fold in terms of weight and cell number compared to in wild-type mice
• spleens and lymph nodes are enlarged up to 30-fold in terms of weight and cell number compared to in wild-type mice
• the spleen marginal zone is disrupted unlike in wild-type mice
• B cells are more resistance than in wild-type mice to Fas-mediated cell death following activation
• activated B cells exhibit enhanced proliferation and survival compared to wild-type cells
• B-2 cell proliferation is enhanced following activation with anti-IgM or lipopolysaccharides unlike in wild-type cells
• 4- to 6-fold at 8 to 12 weeks of age
• 4- to 6-fold at 8 to 12 weeks of age
• 4- to 6-fold at 8 to 12 weeks of age
• 4- to 6-fold at 8 to 12 weeks of age
• more CD4+ T cells produce IFN-gamma and IL-10 but not IL-4 or TNF than wild-type cells
• CD4+T cells from older mice produce more IFN-gamma and IL-10 than CD4+ T cells from younger mice
• activated T cells exhibit enhanced proliferation and survival compared to wild-type cells




Genotype
MGI:3783574
cn15
Allelic
Composition
Gt(ROSA)26Sortm3(CAG-MIR17-92,-EGFP)Rsky/Gt(ROSA)26Sor+
Tg(CD2-icre)4Kio/0
Genetic
Background
involves: C57BL/6 * C57BL/10 * CBA/Ca
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm3(CAG-MIR17-92,-EGFP)Rsky mutation (1 available); any Gt(ROSA)26Sor mutation (510 available)
Tg(CD2-icre)4Kio mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• mice exhibit more CD19+B220loCD5+CD43+CD23- B-1a cells in the spleen and peritoneal cavity compared to in wild-type mice

hematopoietic system
• mice exhibit more CD19+B220loCD5+CD43+CD23- B-1a cells in the spleen and peritoneal cavity compared to in wild-type mice




Genotype
MGI:6360065
cn16
Allelic
Composition
Mir146tm1.1Lfl/Mir146tm1.1Lfl
Tg(CD2-icre)4Kio/0
Genetic
Background
involves: C57BL/6 * C57BL/10 * CBA/Ca
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Mir146tm1.1Lfl mutation (0 available); any Mir146 mutation (7 available)
Tg(CD2-icre)4Kio mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
immune system
• following immunization with sheep red blood cells similar to in B cell conditional knock-outs
• following immunization with sheep red blood cells

hematopoietic system
• following immunization with sheep red blood cells similar to in B cell conditional knock-outs
• following immunization with sheep red blood cells




Genotype
MGI:6160464
cn17
Allelic
Composition
Gimap6tm1.1Gwb/Gimap6tm1.1Gwb
Tg(CD2-icre)4Kio/0
Genetic
Background
involves: C57BL/6 * C57BL/10 * CBA/Ca
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gimap6tm1.1Gwb mutation (0 available); any Gimap6 mutation (8 available)
Tg(CD2-icre)4Kio mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• increased levels of Map1lc3b (particularly the LC3-II variant) protein in Cd4+ T cells and Cd8+ T and B cells isolated from spleen, indicating increased number of autophagosomes
• increased number of autophagosomes per Cd4+ T splenocyte as indicated by electron microscopy
• significant increase in mitochondrial/cytoplasmic volume ratio in Cd4+ T splenocytes as indicated by electron microscopy

cellular
• occasional mitochondrial spheroid observed in Cd4+ T splenocytes by electron microscopy
• significant increase in mitochondrial/cytoplasmic volume ratio in Cd4+ T splenocytes as indicated by electron microscopy
• increased levels of Map1lc3b (particularly the LC3-II variant) protein in Cd4+ T cells and Cd8+ T and B cells isolated from spleen, indicating increased number of autophagosomes
• increased number of autophagosomes per Cd4+ T splenocyte as indicated by electron microscopy
• significant increase in mitochondrial/cytoplasmic volume ratio in Cd4+ T splenocytes as indicated by electron microscopy
• of Cd4+ T splenocytes as indicated by annexin V+ DAPI- staining
• younger age profile of Cd4+ T splenocytes as indicated by Cd24+ staining

hematopoietic system
• increase in cytoplasmic surface area per nucleated Cd4+ T splenocyte as indicated by electron microscopy
• increase in Cd4+ T cells and Cd8+ T splenocyte diameter
• significant reduction in recirculating B cell percentage in bone marrow
• significant increase in percentages and numbers of follicular, marginal zone, T1, T2 and T3 B splenocytes
• significant increase in percentage, but not number, of mature B cells in lymph nodes
• 50-70% reduction in percentage and number of Cd4+ and Cd8+ T cells in spleen and lymph nodes
• Cd4- Cd8-, Cd4+ Cd8+, Cd4+ and Cd8+ T cell percentages in thymus
• shift from Cd62l(high) Cd44(low) to Cd62l(low) Cd44(high) cell surface expression on splenic and lymph node Cd4+ T cells
• reduction in Cd44(high) fraction of splenic and lymph node Cd8+ T cells
• Cd69 surface expression on Cd4+ and Cd8+ T splenocytes
• of Cd4+ T splenocytes as indicated by annexin V+ DAPI- staining
• younger age profile of Cd4+ T splenocytes as indicated by Cd24+ staining

immune system
• increase in cytoplasmic surface area per nucleated Cd4+ T splenocyte as indicated by electron microscopy
• increase in Cd4+ T cells and Cd8+ T splenocyte diameter
• significant reduction in recirculating B cell percentage in bone marrow
• significant increase in percentages and numbers of follicular, marginal zone, T1, T2 and T3 B splenocytes
• significant increase in percentage, but not number, of mature B cells in lymph nodes
• 50-70% reduction in percentage and number of Cd4+ and Cd8+ T cells in spleen and lymph nodes
• Cd4- Cd8-, Cd4+ Cd8+, Cd4+ and Cd8+ T cell percentages in thymus
• shift from Cd62l(high) Cd44(low) to Cd62l(low) Cd44(high) cell surface expression on splenic and lymph node Cd4+ T cells
• reduction in Cd44(high) fraction of splenic and lymph node Cd8+ T cells
• Cd69 surface expression on Cd4+ and Cd8+ T splenocytes
• of Cd4+ T splenocytes as indicated by annexin V+ DAPI- staining
• younger age profile of Cd4+ T splenocytes as indicated by Cd24+ staining




Genotype
MGI:5662109
cn18
Allelic
Composition
Noc2ltm1.1Arte/Noc2ltm1.1Arte
Tg(CD2-icre)4Kio/0
Genetic
Background
involves: C57BL/6 * C57BL/10 * CBA/Ca
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Noc2ltm1.1Arte mutation (0 available); any Noc2l mutation (0 available)
Tg(CD2-icre)4Kio mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
hematopoietic system
• increased apoptosis in DN3 thymocytes
• retention of the DN3 cell population indicating a block between the DN3 and DN4 stages of development
• lack a distinct cortex-medulla compartmentalization
• approximately 98% of cells recovered from the thymi are double negative
• at 5-6 weeks of age
• dramatic reduction in cellularity at 5-6 weeks of age
• decrease in the number of DN3L (larger cycling) cells with a preservation of the DN3E (small, resting G1) population
• severe early involution is seen at 5-6 weeks of age
• dramatic decrease in B220+IgM+ immature B cells in the bone marrow
• developmental block between very early pro-B cells (B220+CD43+CD19-) and later pro-B (B220+CD43+CD19+) stage
• decrease in B220+IgM+ mature B cells
• significant decrease in the B220+CD43- pre-B population
• almost a complete absence of double positive T cells in the thymus
• retention of the DN3 cell population indicating a block between the DN3 and DN4 stages of development
• decrease in the number of TCR-Beta producing cells
• however, the gamma-delta cell population is preserved
• absence of mature splenic T cells at P5
• decrease in the number of single positive CD4+ and CD8+ cells
• decrease in T cells and B220+IgM+ mature B cells

endocrine/exocrine glands
• increased apoptosis in DN3 thymocytes
• lack a distinct cortex-medulla compartmentalization
• approximately 98% of cells recovered from the thymi are double negative
• at 5-6 weeks of age
• dramatic reduction in cellularity at 5-6 weeks of age
• decrease in the number of DN3L (larger cycling) cells with a preservation of the DN3E (small, resting G1) population
• severe early involution is seen at 5-6 weeks of age

immune system
• increased apoptosis in DN3 thymocytes
• retention of the DN3 cell population indicating a block between the DN3 and DN4 stages of development
• lack a distinct cortex-medulla compartmentalization
• approximately 98% of cells recovered from the thymi are double negative
• at 5-6 weeks of age
• dramatic reduction in cellularity at 5-6 weeks of age
• decrease in the number of DN3L (larger cycling) cells with a preservation of the DN3E (small, resting G1) population
• severe early involution is seen at 5-6 weeks of age
• dramatic decrease in B220+IgM+ immature B cells in the bone marrow
• developmental block between very early pro-B cells (B220+CD43+CD19-) and later pro-B (B220+CD43+CD19+) stage
• decrease in B220+IgM+ mature B cells
• significant decrease in the B220+CD43- pre-B population
• almost a complete absence of double positive T cells in the thymus
• retention of the DN3 cell population indicating a block between the DN3 and DN4 stages of development
• decrease in the number of TCR-Beta producing cells
• however, the gamma-delta cell population is preserved
• absence of mature splenic T cells at P5
• decrease in the number of single positive CD4+ and CD8+ cells
• decrease in T cells and B220+IgM+ mature B cells

cellular
• DN3 thymocytes show a block at the G1/S phase of the cell cycle
• increased apoptosis in DN3 thymocytes
• retention of the DN3 cell population indicating a block between the DN3 and DN4 stages of development




Genotype
MGI:4819157
cn19
Allelic
Composition
Zfp36l1tm1.1Tnr/Zfp36l1tm1.1Tnr
Zfp36l2tm1.1Tnr/Zfp36l2tm1.1Tnr
Tg(CD2-icre)4Kio/0
Genetic
Background
involves: C57BL/6 * C57BL/10 * CBA/Ca * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(CD2-icre)4Kio mutation (4 available)
Zfp36l1tm1.1Tnr mutation (0 available); any Zfp36l1 mutation (2 available)
Zfp36l2tm1.1Tnr mutation (0 available); any Zfp36l2 mutation (9 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• by 6 months of age, 90% of the mutant mice die or are humanely killed because of their ill health

neoplasm
• all mutant mice develop thymic tumors
• thymic tumors have high CD8 expression, with variable CD4 expression
• high expression of heat-stable antigen (CD24) but do not have surface expression of the TCR beta-chain (TCRbeta)
• most but not all tumors have intracellular expression of TCRbeta
• Notch1 mutation is present in a minority of tumors and affected mainly the heterodimerization domain (25%) rather than the PEST domain (8%)
• primary tumor cells cultured in vitro are Notch1 dependent and killed by Zfp36l1 re-expression
• development of T cell acute lymphoblastic leukemia
• circulating lymphoblasts in peripheral blood
• tumor cells in thymus, spleen, lymph node and bone marrow
• predominantly oligoclonal
• corresponding to the CD8+ immature single-positive (CD8iSP) and double-positive (DP) stages of thymic development

immune system
• perturbed thymopoiesis before tumor development
• thymic atrophy at 3 and 8 weeks of age
• gradual expansion of the CD8iSP population (CD8+CD4_CD24hi, membrane TCRbeta negative) in both proportion and absolute number by 13 weeks
• less progression from double-negative 2 (DN2) (CD44+CD25+) to DN3 (CD44_CD25+)
• decreased proportion of DN thymocytes with icTCRbeta expression
• only 30% of CD8iSP cells and 90% of DP cells have icTCRbeta expression
• thymic atrophy at 3 and 8 weeks of age
• total thymic cellularity is approximately 50% that of control mice
• many mutant mice have splenomegaly
• many mutant mice have lymphadenopathy

cellular
• increased cellular proliferation by EdU staining in thymic populations from mice aged 5 and 10 weeks old

hematopoietic system
• perturbed thymopoiesis before tumor development
• thymic atrophy at 3 and 8 weeks of age
• gradual expansion of the CD8iSP population (CD8+CD4_CD24hi, membrane TCRbeta negative) in both proportion and absolute number by 13 weeks
• less progression from double-negative 2 (DN2) (CD44+CD25+) to DN3 (CD44_CD25+)
• decreased proportion of DN thymocytes with icTCRbeta expression
• only 30% of CD8iSP cells and 90% of DP cells have icTCRbeta expression
• thymic atrophy at 3 and 8 weeks of age
• total thymic cellularity is approximately 50% that of control mice
• many mutant mice have splenomegaly

endocrine/exocrine glands
• perturbed thymopoiesis before tumor development
• thymic atrophy at 3 and 8 weeks of age
• gradual expansion of the CD8iSP population (CD8+CD4_CD24hi, membrane TCRbeta negative) in both proportion and absolute number by 13 weeks
• less progression from double-negative 2 (DN2) (CD44+CD25+) to DN3 (CD44_CD25+)
• decreased proportion of DN thymocytes with icTCRbeta expression
• only 30% of CD8iSP cells and 90% of DP cells have icTCRbeta expression
• thymic atrophy at 3 and 8 weeks of age
• total thymic cellularity is approximately 50% that of control mice
• all mutant mice develop thymic tumors
• thymic tumors have high CD8 expression, with variable CD4 expression
• high expression of heat-stable antigen (CD24) but do not have surface expression of the TCR beta-chain (TCRbeta)
• most but not all tumors have intracellular expression of TCRbeta
• Notch1 mutation is present in a minority of tumors and affected mainly the heterodimerization domain (25%) rather than the PEST domain (8%)
• primary tumor cells cultured in vitro are Notch1 dependent and killed by Zfp36l1 re-expression

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
acute lymphocytic leukemia DOID:9952 OMIM:247640
OMIM:613065
OMIM:613067
OMIM:615545
J:162388





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
01/14/2020
MGI 6.14
The Jackson Laboratory