Phenotypes associated with this allele

• Allele Symbol: Tg(Foxp3-EGFP/icre)1aJbs
• Allele Name: transgene insertion 1a, Jeffrey Bluestone
• Allele ID: MGI:4430213
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Map4k2^tm1c(KOMP)Wtsi/Map4k2^+ Tg(Foxp3-EGFP/icre)1aJbs/0	B6.Cg-Map4k2^tm1c(KOMP)Wtsi Tg(Foxp3-EGFP/icre)1aJbs	MGI:8399075
cn2	Dicer1^tm1Bdh/Dicer1^tm1Bdh Tg(Foxp3-EGFP/icre)1aJbs/0	involves: 129 * NOD/ShiLt	MGI:3809798

Genotype
MGI:8399075

cn1

• Allelic Composition: Map4k2^{tm1c(KOMP)Wtsi}/Map4k2⁺; Tg(Foxp3-EGFP/icre)1aJbs/0
• Genetic Background: B6.Cg-Map4k2^{tm1c(KOMP)Wtsi} Tg(Foxp3-EGFP/icre)1aJbs

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

immune system

decreased regulatory T cell number ( J:382684 )

• mice show a significant reduction in the population of regulatory T cells (Treg, CD4+FOXP3+) in the spleen

abnormal CD4-positive, CD25-positive, alpha-beta regulatory T cell morphology ( J:382684 )

• splenic CD4+ CD25+ T cells show significantly reduced protein levels of FOXP3 (a Treg master transcription factor)

increased susceptibility to experimental autoimmune encephalomyelitis ( J:382684 )

• in the MOG-induced EAE model, mice exhibit sustained EAE inflammation during the remission phase, with significantly higher clinical scores and serum IL-17A, IL-6, and IFN-gamma levels and a significant reduction in serum IL-10 levels and infiltrating Treg cells in brain tissue, similar to B6.Cg-Tg(Cd4-cre)1Cwi Map4k2^{tm1c(KOMP)Wtsi} mice

hematopoietic system

decreased regulatory T cell number ( J:382684 )

• mice show a significant reduction in the population of regulatory T cells (Treg, CD4+FOXP3+) in the spleen

abnormal CD4-positive, CD25-positive, alpha-beta regulatory T cell morphology ( J:382684 )

• splenic CD4+ CD25+ T cells show significantly reduced protein levels of FOXP3 (a Treg master transcription factor)

neoplasm

abnormal tumor pathology ( J:382684 )

• in the syngeneic KPC pancreatic cancer model, tumor-bearing mice established by s.c. injection of pancreatic cancer cells from KPC (Kras^tm4Tyj/Kras⁺ Trp53^tm2Tyj/Trp53⁺ Tg(Pdx1-cre)6Tuv/0) mice and then i.p. injected with anti-PD-1 antibody show a significant reduction of tumor-infiltrating Treg (CD4+ FOXP3+) cells in tumor tissues; similarly, the % of CTLA4+ CD8+ (exhausted) cytotoxic T cells is also reduced in tumor tissues

• in contrast, the tumor-infiltrating CD8+ T cells are increased, suggesting that MAP4K2 deficiency leads to a reduced Treg population and induction of cytotoxic T cell population, contributing to the enhancement of anticancer immunity

decreased tumor growth/size ( J:382684 )

• in the syngeneic KPC pancreatic cancer model, tumor-bearing mice established by s.c. injection of pancreatic cancer cells from KPC mice and then i.p. injected with anti-PD-1 antibody show a significant decrease in tumor volume relative to anti-PD-1-treated control mice

Genotype
MGI:3809798

cn2

• Allelic Composition: Dicer1^tm1Bdh/Dicer1^tm1Bdh; Tg(Foxp3-EGFP/icre)1aJbs/0
• Genetic Background: involves: 129 * NOD/ShiLt

mortality/aging

premature death ( J:138808 )

• all mice die by 6-8 weeks of age

growth/size/body

weight loss ( J:138808 )

• aging animals display weight loss

enlarged spleen ( J:138808 )

• observed in all aging animals (>5 weeks of age)

behavior/neurological

abnormal behavior ( J:138808 )

• aging animals display reduced mobility

immune system

enlarged spleen ( J:138808 )

• observed in all aging animals (>5 weeks of age)

abnormal effector T cell morphology ( J:138808 )

• number of CTLA4-expressing CD4+ Foxp3- effector T cells increase to >50% of splenic and >70% of lymph node CD4+ T cells compared to <10% in wild-type littermates

abnormal regulatory T cell morphology ( J:138808 )

• T reg cells have a higher percentage of CD103+ T cells and greater number of CD62^lo cells

decreased regulatory T cell number ( J:138808 )

• percentage of regulatory T (T reg) cells in spleen and peripheral blood is reduced to 33% of controls

abnormal splenic cell ratio ( J:138808 )

• dramatic increase in splenic T cells is seen in 4-6 week old mice relative to controls

abnormal CD4-positive, alpha-beta T cell physiology ( J:138808 )

• many effector T cells have high levels of Il4, Il10 and interferon gamma, Ifng whereas <1% of cells from wild-type express Il4, Il10, Il17 or Ifng

abnormal regulatory T cell physiology ( J:138808 )

• CD4+ Foxp3+ T regs have a more prominent activated phenotype (increased expression of CD25, CTLA4 and glucocorticoid-induced TNFR)

abnormal lymph node cell ratio ( J:138808 )

• dramatic increase in lymph node T cells is seen in 4-6 week old mice; however percentage of regulatory T cells is maintained

enlarged lymph nodes ( J:138808 )

• observed in all aging animals (>5 weeks of age)

liver inflammation ( J:138808 )

• tissue displays extensive mononuclear cell infiltration

lung inflammation ( J:138808 )

• tissue displays extensive mononuclear cell infiltration

• tissue has dense predominantly peribronchovascular infiltrates, composed of CD4+ and Cd8+ T cells

hematopoietic system

enlarged spleen ( J:138808 )

• observed in all aging animals (>5 weeks of age)

abnormal effector T cell morphology ( J:138808 )

• number of CTLA4-expressing CD4+ Foxp3- effector T cells increase to >50% of splenic and >70% of lymph node CD4+ T cells compared to <10% in wild-type littermates

abnormal regulatory T cell morphology ( J:138808 )

• T reg cells have a higher percentage of CD103+ T cells and greater number of CD62^lo cells

decreased regulatory T cell number ( J:138808 )

• percentage of regulatory T (T reg) cells in spleen and peripheral blood is reduced to 33% of controls

abnormal splenic cell ratio ( J:138808 )

• dramatic increase in splenic T cells is seen in 4-6 week old mice relative to controls

abnormal CD4-positive, alpha-beta T cell physiology ( J:138808 )

• many effector T cells have high levels of Il4, Il10 and interferon gamma, Ifng whereas <1% of cells from wild-type express Il4, Il10, Il17 or Ifng

abnormal regulatory T cell physiology ( J:138808 )

• CD4+ Foxp3+ T regs have a more prominent activated phenotype (increased expression of CD25, CTLA4 and glucocorticoid-induced TNFR)

liver/biliary system

liver inflammation ( J:138808 )

• tissue displays extensive mononuclear cell infiltration

respiratory system

lung inflammation ( J:138808 )

• tissue displays extensive mononuclear cell infiltration

• tissue has dense predominantly peribronchovascular infiltrates, composed of CD4+ and Cd8+ T cells

skeleton

kyphosis ( J:138808 )

• seen in aging animals