Phenotypes associated with this allele

• Allele Symbol: Arfgap2^{tm1c(EUCOMM)Hmgu}
• Allele Name: targeted mutation 1c, Helmholtz Zentrum Muenchen GmbH
• Allele ID: MGI:8163548
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Arfgap2^tm1c(EUCOMM)Hmgu/Arfgap2^tm1c(EUCOMM)Hmgu Lyz2^tm1(cre)Ifo/Lyz2^+	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * C57BL/6N	MGI:8207789
cn2	Arfgap2^tm1c(EUCOMM)Hmgu/Arfgap2^tm1c(EUCOMM)Hmgu Tg(CAG-cre/Esr1*)5Amc/0	involves: 129S4/SvJae * C57BL/6J * C57BL/6N	MGI:8207782
cn3	Arfgap2^tm1c(EUCOMM)Hmgu/Arfgap2^tm1c(EUCOMM)Hmgu Tg(Cd4-cre)1Cwi/0	involves: 129S4/SvJae * C57BL/6J * C57BL/6N	MGI:8207790
cn4	Arfgap2^tm1c(EUCOMM)Hmgu/Arfgap2^tm1c(EUCOMM)Hmgu Commd10^Tg(Vav1-icre)A2Kio/Commd10^+	involves: 129S4/SvJae * C57BL/6J * C57BL/6N * C57BL/10 * CBA/Ca	MGI:8207800
cn5	Arfgap2^tm1c(EUCOMM)Hmgu/Arfgap2^tm1c(EUCOMM)Hmgu Sting1^em1Jmin/Sting1^em1Jmin Commd10^Tg(Vav1-icre)A2Kio/Commd10^+	Not Specified	MGI:8207802

Genotype
MGI:8207789

cn1

• Allelic Composition: Arfgap2^{tm1c(EUCOMM)Hmgu}/Arfgap2^{tm1c(EUCOMM)Hmgu}; Lyz2^tm1(cre)Ifo/Lyz2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * C57BL/6N

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

immune system

immune system phenotype ( J:363611 )

N • in the absence of STING activation, mice show normal populations of neutrophils, monocytes, dendritic cells, and macrophages in spleen

Genotype
MGI:8207782

cn2

• Allelic Composition: Arfgap2^{tm1c(EUCOMM)Hmgu}/Arfgap2^{tm1c(EUCOMM)Hmgu}; Tg(CAG-cre/Esr1*)5Amc/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * C57BL/6N

immune system

immune system phenotype ( J:363611 )

N • in the absence of STING activation, primary bone marrow derived macrophages (BMDMs) from 4-hydroxytamoxifen-treated mice show normal macrophage activation with no differences in LPS + IFN-gamma-induced M1 polarization or IL-4-induced M2 polarization relative to control BMDMs

N • after a 24-h stimulation with exogenous IFN-beta, primary BMDMs from 4-hydroxytamoxifen-treated mice show normal expression of IFN-stimulated genes (Ifi44, Ifit1, Isg15 and Rsad2), indicating functional type I IFN receptor signaling

abnormal macrophage activation involved in immune response ( J:363611 )

• 3 h after STING activation with diABZI (a cell-permeable STING agonist), BMDMs from 4-hydroxytamoxifen-treated mice show a severe reduction in the expression of IFN-stimulated genes (Ifi44, Ifit1, Isg15 and Rsad2) and downstream activation of TBK1 and IRF3

• RNA-seq analysis shows an almost complete loss of STING-induced IFN-stimulated genes (ISGs) in 4-hydroxytamoxifen-treated BMDMs

• 48 h after STING activation with diABZI, 4-hydroxytamoxifen-treated BMDMs infected with West Nile virus (WNV) show only a 2.3-fold reduction in WNV growth versus a 14.-fold reduction in WNV-infected control BMDMs

decreased macrophage cytokine production ( J:363611 )

• 24 h after STING activation with diABZI, 4-hydroxytamoxifen-treated BMDMs show a severe reduction in cytokine secretion downstream of STING (CCL3/MIP1-alpha, CCL4/ MIP1-beta, IL-6 and CCL5) relative to control BMDMs

• however, 4-hydroxytamoxifen-treated BMDMs show normal cytokine secretion in response to challenge with LPS (a TLR4 agonist), and normal expression of Rsad2 and Isg15 after treatment with 5'ppp-dsRNA (a RIG-I ligand), in response to poly(I:C) (a TLR3 ligand), or during infection with encephalomyocarditis virus (EMCV) which activates the type I IFN response via RNA sensor MDA5

decreased level of surface class I molecules ( J:363611 )

• 24 h after STING activation with diABZI, BMDMs from 4-hydroxytamoxifen-treated mice show diminished STING-mediated MHC class I upregulation relative to control BMDMs

decreased level of surface class II molecules ( J:363611 )

• 24 h after STING activation with diABZI, BMDMs from 4-hydroxytamoxifen-treated mice show diminished STING-mediated MHC class II upregulation relative to control BMDMs

decreased interferon-beta secretion ( J:363611 )

• 3 h after STING activation with diABZI, BMDMs from 4-hydroxytamoxifen-treated mice show a ~13-fold reduction in IFN-beta secretion

• however, IFN-alpha secretion after STING activation is similar to that in control BMDMs

decreased interleukin-6 secretion ( J:363611 )

• 24 h after STING activation with diABZI, 4-hydroxytamoxifen-treated BMDMs show a severe reduction in IL-6 secretion relative to control BMDMs

• however, IL-6 secretion is normal in 4-hydroxytamoxifen-treated BMDMs challenged with LPS (a TLR4 agonist)

hematopoietic system

abnormal macrophage activation involved in immune response ( J:363611 )

• 3 h after STING activation with diABZI (a cell-permeable STING agonist), BMDMs from 4-hydroxytamoxifen-treated mice show a severe reduction in the expression of IFN-stimulated genes (Ifi44, Ifit1, Isg15 and Rsad2) and downstream activation of TBK1 and IRF3

• RNA-seq analysis shows an almost complete loss of STING-induced IFN-stimulated genes (ISGs) in 4-hydroxytamoxifen-treated BMDMs

• 48 h after STING activation with diABZI, 4-hydroxytamoxifen-treated BMDMs infected with West Nile virus (WNV) show only a 2.3-fold reduction in WNV growth versus a 14.-fold reduction in WNV-infected control BMDMs

decreased macrophage cytokine production ( J:363611 )

• 24 h after STING activation with diABZI, 4-hydroxytamoxifen-treated BMDMs show a severe reduction in cytokine secretion downstream of STING (CCL3/MIP1-alpha, CCL4/ MIP1-beta, IL-6 and CCL5) relative to control BMDMs

• however, 4-hydroxytamoxifen-treated BMDMs show normal cytokine secretion in response to challenge with LPS (a TLR4 agonist), and normal expression of Rsad2 and Isg15 after treatment with 5'ppp-dsRNA (a RIG-I ligand), in response to poly(I:C) (a TLR3 ligand), or during infection with encephalomyocarditis virus (EMCV) which activates the type I IFN response via RNA sensor MDA5

Genotype
MGI:8207790

cn3

• Allelic Composition: Arfgap2^{tm1c(EUCOMM)Hmgu}/Arfgap2^{tm1c(EUCOMM)Hmgu}; Tg(Cd4-cre)1Cwi/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * C57BL/6N

immune system

immune system phenotype ( J:363611 )

N • in the absence of STING activation, mice show no significant differences in the frequencies of thymocytes, splenic T cells, and splenic myeloid cells relative to control mice

N • splenocytes show normal frequencies of CD3+ (T cells), CD19+ (B cells) and CD3- (non-T non-B cells) relative to CD45+ cells; normal CD4+ and CD8+ T cells relative to total CD3+ cells; normal central memory and effector memory CD4+ and CD8+ T cells; and normal FoxP3+ CD4+ regulatory T cells (Tregs)

N • moreover, splenocytes show normal frequencies of Ly6G+CD11b+ neutrophils relative to total CD3- splenocytes; normal Ly6C^hi CD11b+ monocytes relative to total Ly6G- splenocytes; and normal F4/80^midCD11b+ macrophages and F4/80^hiCD11b- red pulp macrophages relative to total Ly6C^lo splenocytes

N • thymocytes show normal frequencies of double-negative (DN), double-positive (DP), and single-positive CD4 and CD8 T cells and normal frequencies of DN subsets

Genotype
MGI:8207800

cn4

• Allelic Composition: Arfgap2^{tm1c(EUCOMM)Hmgu}/Arfgap2^{tm1c(EUCOMM)Hmgu}; Commd10^{Tg(Vav1-icre)A2Kio}/Commd10⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * C57BL/6N * C57BL/10 * CBA/Ca

immune system

immune system phenotype ( J:363611 )

N • in the absence of STING activation, mice show normal frequency of FoxP3+ regulatory T cells (Tregs) relative to CD4+ T cells in spleen; normal numbers of CD4+ effector T cells (Teff, CD3+ CD4+CD44+CD62L-); normal ratio of Teff to Treg cells; and normal frequency of naive (CD3+CD4+CD44-CD62L+), memory (CD3+CD4+ CD44+CD62L+), and effector CD4+ T cells in spleen relative to control mice

Genotype
MGI:8207802

cn5

• Allelic Composition: Arfgap2^{tm1c(EUCOMM)Hmgu}/Arfgap2^{tm1c(EUCOMM)Hmgu}; Sting1^em1Jmin/Sting1^em1Jmin; Commd10^{Tg(Vav1-icre)A2Kio}/Commd10⁺
• Genetic Background: Not Specified

immune system

decreased effector memory CD4-positive, alpha-beta T cell number ( J:363611 )

• mice show a significant decrease in the numbers of CD4+ effector T cells (Teff, CD3+ CD4+CD44+ CD62L-) and the frequency of effector CD4+ T cells, relative to CD4+ T cells, in spleen

increased CD4-positive, alpha-beta T cell number ( J:363611 )

• mice show a significant increase in the frequency of CD4+ T cells, relative to total CD3+ cells, and of naive CD4+ T cells (CD3+ CD4+ CD44-CD62L+), relative to CD4+ T cells, in spleen

increased CD4-positive, alpha-beta memory T cell number ( J:363611 )

• mice show a significant increase in the frequency of memory CD4+ T cells (CD3+ CD4+CD44+ CD62L+), relative to CD4+ T cells, in spleen

decreased CD8-positive, alpha-beta T cell number ( J:363611 )

• mice show a significant decrease in the frequency of CD8+ T cells, relative to total CD3+ cells, in spleen

increased regulatory T cell number ( J:363611 )

• mice show a significant increase in the frequency of FoxP3+ regulatory T cells (Tregs), relative to CD4+ T cells, in spleen

abnormal splenic cell ratio ( J:363611 )

• mice show a significant increase in the ratio of CD4+ to CD8+ T cells along with a significant decrease in the ratio of Teff to Treg cells in spleen

decreased interferon-gamma secretion ( J:363611 )

• mice show a 6-fold decrease of interferon-gamma in lung homogenates

decreased interleukin-1 beta secretion ( J:363611 )

• mice show a 4-fold decrease of interleukin-1 beta levels in lung homogenates

decreased susceptibility to autoimmune disorder ( J:363611 )

• mice show marked amelioration of STING-associated autoinflammation and lung disease with ~4- and ~6-fold reductions in levels of IL-1beta and IFN-gamma, as well as ~170-, ~30, and ~12-fold reductions in mRNA levels of Cxcl9, Cxcl10, and Ccl5, respectively, with corresponding reductions in chemokine protein levels in the lungs relative to SAVI mice homozygous for Arfgap2 but without Cre

hematopoietic system

decreased effector memory CD4-positive, alpha-beta T cell number ( J:363611 )

• mice show a significant decrease in the numbers of CD4+ effector T cells (Teff, CD3+ CD4+CD44+ CD62L-) and the frequency of effector CD4+ T cells, relative to CD4+ T cells, in spleen

increased CD4-positive, alpha-beta T cell number ( J:363611 )

• mice show a significant increase in the frequency of CD4+ T cells, relative to total CD3+ cells, and of naive CD4+ T cells (CD3+ CD4+ CD44-CD62L+), relative to CD4+ T cells, in spleen

increased CD4-positive, alpha-beta memory T cell number ( J:363611 )

• mice show a significant increase in the frequency of memory CD4+ T cells (CD3+ CD4+CD44+ CD62L+), relative to CD4+ T cells, in spleen

decreased CD8-positive, alpha-beta T cell number ( J:363611 )

• mice show a significant decrease in the frequency of CD8+ T cells, relative to total CD3+ cells, in spleen

increased regulatory T cell number ( J:363611 )

• mice show a significant increase in the frequency of FoxP3+ regulatory T cells (Tregs), relative to CD4+ T cells, in spleen

abnormal splenic cell ratio ( J:363611 )

• mice show a significant increase in the ratio of CD4+ to CD8+ T cells along with a significant decrease in the ratio of Teff to Treg cells in spleen