Phenotypes associated with this allele

• Allele Symbol: Cd274^tm1Lpc
• Allele Name: targeted mutation 1, Lieping Chen
• Allele ID: MGI:3043876
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cd274^tm1Lpc/Cd274^tm1Lpc	B6.129S-Cd274^tm1Lpc	MGI:3043881
hm2	Cd274^tm1Lpc/Cd274^tm1Lpc	C.129S-Cd274^tm1Lpc	MGI:5298404
hm3	Cd274^tm1Lpc/Cd274^tm1Lpc	involves: 129S/SvEv	MGI:5298402
hm4	Cd274^tm1Lpc/Cd274^tm1Lpc	involves: 129S/SvEv * C57BL/6	MGI:5298403

Genotype
MGI:3043881

hm1

• Allelic Composition: Cd274^tm1Lpc/Cd274^tm1Lpc
• Genetic Background: B6.129S-Cd274^tm1Lpc

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

immune system

decreased T cell apoptosis ( J:89781 )

• homozygotes display reduced apoptosis of SEB-activated CD8⁺ T cells in the liver, but not in the lymph nodes, kidney, or lung

• in an OT-1 TCR transgenic T cell-transfer system, homozygotes display a significantly reduced apoptosis of activated OT-1 CD8⁺ cells in the liver on day 5 after OVA peptide injection (11.2% vs 49.2% in wild-type controls)

• however, no significant differences in intrahepatic CD8⁺ T cell apoptosis are observed in naive homozygotes relative to wild-type controls

increased CD8-positive, alpha-beta T cell number ( J:89781 )

• homozygotes display spontaneous accumulation of CD8⁺ T cells in the liver (average ratio of intrahepatic CD8⁺ to CD4⁺ T cells is equal to 1.6 vs 0.46 in wild-type mice) and kidney (9.4% vs 3.2% in wild-type mice), with only a marginal increase observed in lung (11.6% vs 7.1% in wild-type mice)

• however, numbers of intrahepatic CD4⁺ T cells and B220⁺ B cells are not significantly altered

increased activated T cell number ( J:89781 )

• naive homozygotes show a significant accumulation of activated CD8⁺ T cells in the liver as shown by surface marker expression analysis, with no differences noted in the lymph nodes

• 55.9% of mutant intrahepatic CD8⁺ T cells are CD62L^low relative to 12.7% in wild-type controls

• 85.6% of mutant intrahepatic CD8⁺ T cells are CD45RB^low relative to 12.3% in wild-type controls

• however, no differences in the expression of CD25 or CD44 are observed relative to wild-type controls

abnormal CD8-positive, alpha-beta T cell physiology ( J:89781 , J:267938 )

• following stimulation with staphylococcal enetrotoxin B (SEB), homozygotes show a normal proliferation phase but display impaired deletion of SEB-activated CD8⁺ Vbeta8⁺ T cells in the liver on day 7 of the contraction phase, when SEB-primed T cells are normally reduced by apoptosis (J:89781)

• following transfer of wild-type CD8⁺ OT-1 T cells and subsequent challenge with OVA peptide, homozygotes show significant accumulation and decreased apoptosis of activated CD8⁺ T cells in the liver (J:89781)

• when naive OT-1 CD8+ T cells are cultured on mutant liver sinusoidal endothelial cells (LSECs) in the presence of OVA antigen, LSEC-primed CD8+ T cells show a marked reduction in mRNA expression of Arl4d (ADP-ribosylation factor-like 4D) and significantly increased IL-2 production (J:267938)

• moreover, LSEC-primed CD8+ T cells show high levels of Akt phosphorylation (pAkt), indicating an inverse correlation of Arl4d expression with the amount of pAkt in activated T cells (J:267938)

increased interleukin-2 secretion ( J:267938 )

• when naive OT-1 CD8+ T cells are cultured on mutant LSECs in the presence of OVA antigen, LSEC-stimulated CD8+ T cells with low Arl4d mRNA content show a significant increase in antigen-induced IL-2 production

increased susceptibility to autoimmune disorder ( J:89781 )

• in a model of experimental (ConA-induced) autoimmune hepatitis, homozygotes display accelerated hepatocyte damage and necrosis, higher serum GTP levels, increased infiltration of mononuclear cells and reduced apoptosis of CD8⁺ T cells in the liver relative to wild-type controls

• 40% of homozygotes die upon induction relative to only 10% of wild-type controls

hematopoietic system

hematopoietic system phenotype ( J:89781 )

N • at 8-12 weeks of age, naive homozygotes display normal T cell populations in the thymus, spleen and lymph nodes relative to wild-type controls

decreased T cell apoptosis ( J:89781 )

• homozygotes display reduced apoptosis of SEB-activated CD8⁺ T cells in the liver, but not in the lymph nodes, kidney, or lung

• in an OT-1 TCR transgenic T cell-transfer system, homozygotes display a significantly reduced apoptosis of activated OT-1 CD8⁺ cells in the liver on day 5 after OVA peptide injection (11.2% vs 49.2% in wild-type controls)

• however, no significant differences in intrahepatic CD8⁺ T cell apoptosis are observed in naive homozygotes relative to wild-type controls

increased CD8-positive, alpha-beta T cell number ( J:89781 )

• homozygotes display spontaneous accumulation of CD8⁺ T cells in the liver (average ratio of intrahepatic CD8⁺ to CD4⁺ T cells is equal to 1.6 vs 0.46 in wild-type mice) and kidney (9.4% vs 3.2% in wild-type mice), with only a marginal increase observed in lung (11.6% vs 7.1% in wild-type mice)

• however, numbers of intrahepatic CD4⁺ T cells and B220⁺ B cells are not significantly altered

increased activated T cell number ( J:89781 )

• naive homozygotes show a significant accumulation of activated CD8⁺ T cells in the liver as shown by surface marker expression analysis, with no differences noted in the lymph nodes

• 55.9% of mutant intrahepatic CD8⁺ T cells are CD62L^low relative to 12.7% in wild-type controls

• 85.6% of mutant intrahepatic CD8⁺ T cells are CD45RB^low relative to 12.3% in wild-type controls

• however, no differences in the expression of CD25 or CD44 are observed relative to wild-type controls

abnormal CD8-positive, alpha-beta T cell physiology ( J:89781 , J:267938 )

• following stimulation with staphylococcal enetrotoxin B (SEB), homozygotes show a normal proliferation phase but display impaired deletion of SEB-activated CD8⁺ Vbeta8⁺ T cells in the liver on day 7 of the contraction phase, when SEB-primed T cells are normally reduced by apoptosis (J:89781)

• following transfer of wild-type CD8⁺ OT-1 T cells and subsequent challenge with OVA peptide, homozygotes show significant accumulation and decreased apoptosis of activated CD8⁺ T cells in the liver (J:89781)

• when naive OT-1 CD8+ T cells are cultured on mutant liver sinusoidal endothelial cells (LSECs) in the presence of OVA antigen, LSEC-primed CD8+ T cells show a marked reduction in mRNA expression of Arl4d (ADP-ribosylation factor-like 4D) and significantly increased IL-2 production (J:267938)

• moreover, LSEC-primed CD8+ T cells show high levels of Akt phosphorylation (pAkt), indicating an inverse correlation of Arl4d expression with the amount of pAkt in activated T cells (J:267938)

cellular

decreased T cell apoptosis ( J:89781 )

• homozygotes display reduced apoptosis of SEB-activated CD8⁺ T cells in the liver, but not in the lymph nodes, kidney, or lung

• in an OT-1 TCR transgenic T cell-transfer system, homozygotes display a significantly reduced apoptosis of activated OT-1 CD8⁺ cells in the liver on day 5 after OVA peptide injection (11.2% vs 49.2% in wild-type controls)

• however, no significant differences in intrahepatic CD8⁺ T cell apoptosis are observed in naive homozygotes relative to wild-type controls

Genotype
MGI:5298404

hm2

• Allelic Composition: Cd274^tm1Lpc/Cd274^tm1Lpc
• Genetic Background: C.129S-Cd274^tm1Lpc

immune system

immune system phenotype ( J:165841 )

N • mice exhibit normal B cell development and response to external stimuli

increased T cell proliferation ( J:165841 )

• in CD4+ T cells from mice treated with PG-dimethyl-dioctadecyl-ammonium bromide (DDA)

decreased germinal center B cell number ( J:165841 )

• after the second PG-DDA immunization

decreased plasma cell number ( J:165841 )

• after the second PG-DDA immunization

decreased T-helper 17 cell number ( J:165841 )

• in mice treated with PG-dimethyl-dioctadecyl-ammonium

decreased IgG1 level ( J:165841 )

• in mice treated with PG-dimethyl-dioctadecyl-ammonium

decreased IgG2a level ( J:165841 )

• in mice treated with PG-dimethyl-dioctadecyl-ammonium

abnormal T follicular helper cell physiology ( J:165841 )

• hyperactived in mice following after the second PG-DDA immunization

abnormal regulatory T cell physiology ( J:165841 )

• regulatory T cells from mice treated with PG-dimethyl-dioctadecyl-ammonium exhibit a more active phenotype than wild-type cells

increased interferon-gamma secretion ( J:165841 )

• in T cells from mice treated with PG-dimethyl-dioctadecyl-ammonium

decreased interleukin-17 secretion ( J:165841 )

• in T cells from mice treated with PG-dimethyl-dioctadecyl-ammonium

increased interleukin-4 secretion ( J:165841 )

• in T cells from mice treated with PG-dimethyl-dioctadecyl-ammonium

increased susceptibility to induced arthritis ( J:165841 )

• mice treated with PG-dimethyl-dioctadecyl-ammonium bromide (DDA) develop more aggressive and severe arthritis with earlier onset compared with wild-type mice

• transplantation experiments indicates that non-B and non-T cells are required for development of induced arthritis

skeleton

increased susceptibility to induced arthritis ( J:165841 )

• mice treated with PG-dimethyl-dioctadecyl-ammonium bromide (DDA) develop more aggressive and severe arthritis with earlier onset compared with wild-type mice

• transplantation experiments indicates that non-B and non-T cells are required for development of induced arthritis

hematopoietic system

increased T cell proliferation ( J:165841 )

• in CD4+ T cells from mice treated with PG-dimethyl-dioctadecyl-ammonium bromide (DDA)

decreased germinal center B cell number ( J:165841 )

• after the second PG-DDA immunization

decreased plasma cell number ( J:165841 )

• after the second PG-DDA immunization

decreased T-helper 17 cell number ( J:165841 )

• in mice treated with PG-dimethyl-dioctadecyl-ammonium

decreased IgG1 level ( J:165841 )

• in mice treated with PG-dimethyl-dioctadecyl-ammonium

decreased IgG2a level ( J:165841 )

• in mice treated with PG-dimethyl-dioctadecyl-ammonium

abnormal T follicular helper cell physiology ( J:165841 )

• hyperactived in mice following after the second PG-DDA immunization

abnormal regulatory T cell physiology ( J:165841 )

• regulatory T cells from mice treated with PG-dimethyl-dioctadecyl-ammonium exhibit a more active phenotype than wild-type cells

cellular

increased T cell proliferation ( J:165841 )

• in CD4+ T cells from mice treated with PG-dimethyl-dioctadecyl-ammonium bromide (DDA)

Genotype
MGI:5298402

hm3

• Allelic Composition: Cd274^tm1Lpc/Cd274^tm1Lpc
• Genetic Background: involves: 129S/SvEv

immune system

abnormal chemokine secretion ( J:158023 )

• following chronic constriction injury, sciatic nerves exhibit a greater increase in CCL2 levels compared with wild-type nerves

increased tumor necrosis factor secretion ( J:158023 )

• following chronic constriction injury, sciatic nerves exhibit a greater increase in TNF-alpha levels compared with wild-type nerves

behavior/neurological

hyperresponsive to tactile stimuli ( J:158023 )

• following chronic constriction injury

homeostasis/metabolism

increased susceptibility to injury ( J:158023 )

• following chronic constriction injury, sciatic nerves exhibit a greater increase in TNF-alpha and CCL2 levels and increased mechanical hyperalgesia compared with wild-type nerves

• however, mice exhibit normal myelination, fiber caliber, and nerve structure

Genotype
MGI:5298403

hm4

• Allelic Composition: Cd274^tm1Lpc/Cd274^tm1Lpc
• Genetic Background: involves: 129S/SvEv * C57BL/6

mortality/aging

increased susceptibility to bacterial infection induced morbidity/mortality ( J:162539 )

• following primary, but not secondary, Salmonella infection

decreased susceptibility to Riboviria infection induced morbidity/mortality ( J:136330 )

• in mice infected with rabies virus

immune system

decreased T cell apoptosis ( J:136330 )

• of CD8+ T cells in mice infected with rabies virus

abnormal T cell morphology ( J:136330 )

• 10 days post-infection with rabies virus, mice exhibit increased migratory CD3+ T cell and CD8+ T cells into the nervous system compared with wild-type mice

abnormal T-helper 1 cell differentiation ( J:162539 )

• impaired after primary Salmonella infection

decreased T helper 1 cell number ( J:162539 )

• after primary Salmonella infection

increased T cell number ( J:142815 )

• increased IFN-gamma T cells following induction of experimental autoimmune encephalomyelitis

increased CD8-positive, alpha-beta T cell number ( J:152305 )

• mice treated with pIpC and immunized with ovalbumin exhibit a 2-fold increase in ovalbumin antigen-specific and ovalbumin-reactive CD8 T cells compared with wild-type mice

increased IgG1 level ( J:162539 )

• slightly 5 weeks after primary Salmonella infection

increased IgG2c level ( J:162539 )

• 5 weeks after primary Salmonella infection

abnormal dendritic cell physiology ( J:152305 )

• dendritic cells from mice treated with pIpC and immunized with ovalbumin induce 2- to 3-fold more ovalbumin-specific (Tet+) CD8 T cells compared with wild-type cells

• pIpC-stimulated bone marrow-derived dendritic cells induce a 3-fold increase in ovalbumin-specific CD8 T cells compared with wild-type cells

• pIpC-activated ovalbumin-pulsed dendritic cells suppress tumor growth more than wild-type mice

increased susceptibility to experimental autoimmune encephalomyelitis ( J:142815 )

• with increased IFN-gamma T cells

increased susceptibility to bacterial infection ( J:162539 )

• following primary Salmonella infection, mice exhibit increased lethality, bacterial colonization of the liver after 5 weeks, and IgG2c and IgG1 response after 5 weeks and impaired Th1 cells development and reduced multifunctional Th1 cells compared with wild-type mice

• however, mice exhibit normal response to secondary infection and clonal expansion of Salmonella-specific CD4 T cells

increased susceptibility to bacterial infection induced morbidity/mortality ( J:162539 )

• following primary, but not secondary, Salmonella infection

decreased susceptibility to Riboviria infection ( J:136330 )

• mice infected with rabies virus exhibit reduced clinical signs of encephalitis, improved survival, increased CD8+ and CD3+ T cell migration into the nervous system, and reduced CD8+ T cell apoptosis compared with wild-type mice

decreased susceptibility to Riboviria infection induced morbidity/mortality ( J:136330 )

• in mice infected with rabies virus

cellular

decreased T cell apoptosis ( J:136330 )

• of CD8+ T cells in mice infected with rabies virus

hematopoietic system

decreased T cell apoptosis ( J:136330 )

• of CD8+ T cells in mice infected with rabies virus

abnormal T cell morphology ( J:136330 )

• 10 days post-infection with rabies virus, mice exhibit increased migratory CD3+ T cell and CD8+ T cells into the nervous system compared with wild-type mice

abnormal T-helper 1 cell differentiation ( J:162539 )

• impaired after primary Salmonella infection

decreased T helper 1 cell number ( J:162539 )

• after primary Salmonella infection

increased T cell number ( J:142815 )

• increased IFN-gamma T cells following induction of experimental autoimmune encephalomyelitis

increased CD8-positive, alpha-beta T cell number ( J:152305 )

• mice treated with pIpC and immunized with ovalbumin exhibit a 2-fold increase in ovalbumin antigen-specific and ovalbumin-reactive CD8 T cells compared with wild-type mice

increased IgG1 level ( J:162539 )

• slightly 5 weeks after primary Salmonella infection

increased IgG2c level ( J:162539 )

• 5 weeks after primary Salmonella infection