Phenotypes associated with this allele

• Allele Symbol: Cd276^tm1Mak
• Allele Name: targeted mutation 1, Tak Mak
• Allele ID: MGI:3033707
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cd276^tm1Mak/Cd276^tm1Mak	C.129P2-Cd276^tm1Mak	MGI:3033860
hm2	Cd276^tm1Mak/Cd276^tm1Mak	involves: 129P2/OlaHsd * C57BL/6	MGI:3033710

Genotype
MGI:3033860

hm1

• Allelic Composition: Cd276^tm1Mak/Cd276^tm1Mak
• Genetic Background: C.129P2-Cd276^tm1Mak

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

immune system

abnormal T-helper 1 physiology ( J:84973 )

• homozygotes develop more severe T helper 1 (TH1)-mediated lung inflammation than wild-type controls

increased interferon-gamma secretion ( J:84973 )

• homozygotes sensitized in T_H1 conditions show a 6-fold increase of IFN-gamma levels in BAL fluid relative to wild-type controls

• when restimulated in vitro with OVA, pulmonary lymph node cell cultures derived from mutant mice sensitized in T_H1 conditions produce ~3 times more IFN-gamma than wild-type cultures, indicating enhanced T_H1 effector activity

increased inflammatory response ( J:84973 )

• upon OVA sensitization, homozygotes develop more severe airway inflammation than wild-type controls in T helper 1 (T_H1) polarizing conditions (GM-CSF plus IL-12), as shown by a 3-fold increase in the number of activated (CD69⁺) CD4 and CD8 T cells in lung, a 6-fold rise in IFN-gamma levels in BAL fluid, and a 3-fold increase in IFN-gamma levels in pulmonary lymph node cell cultures from mice sensitized in T_H1 conditions

hematopoietic system

abnormal T-helper 1 physiology ( J:84973 )

• homozygotes develop more severe T helper 1 (TH1)-mediated lung inflammation than wild-type controls

Genotype
MGI:3033710

hm2

• Allelic Composition: Cd276^tm1Mak/Cd276^tm1Mak
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

immune system

immune system phenotype ( J:84973 )

N • following injection of lymphocytic choriomeningitis virus (LCMV) into the hind footpads, homozygotes show a normal CTL-mediated hypersensitivity reaction, with no differences in the extent and kinetics of footpad swelling relative to wild-type controls

N • surprisingly, homozygotes display normal antiviral CTL responses to LCMV, influenza virus and vesicular stomatitis virus relative to wild-type controls

increased T cell proliferation ( J:84973 )

• in MLR experiments, mutant irradiated B lymphoblasts (H-2^b/b) show a 2-fold increase in their capacity to stimulate alloreactive T cells (both CD4 and CD8 populations) derived from BALB/c mice (H-2^d/d) relative to wild-type B lymphoblasts

abnormal T-helper 1 physiology ( J:84973 )

• homozygotes develop more severe T helper 1 (T_H1)-mediated lung inflammation than wild-type controls

• in contrast, T_H2-mediated airway inflammation is similar to that in wild-type controls

increased susceptibility to experimental autoimmune encephalomyelitis ( J:84973 )

• homozygotes develop experimental autoimmune encephalomyelitis several days earlier than wild-type controls

• however, no differences in mean clinical scores are noted beyond day 20 and the rates of disease incidence are similar to those in wild-type controls

increased anti-single stranded DNA antibody level ( J:84973 )

• starting at ~17 months of age, homozygotes display significantly higher levels of serum autoantibodies to single-stranded DNA than wild-type controls

• however, spontaneous autoimmunity does not result in immune complex deposition in the glomeruli or lymphocytic infiltration into multiple organs

increased inflammatory response ( J:84973 )

• upon OVA sensitization, homozygotes develop more severe airway inflammation than wild-type controls in T helper 1 (T_H1) polarizing conditions (GM-CSF plus IL-12), as shown by significantly increased total immune-inflammatory, lymphocyte and macrophage cell counts in the BAL fluid (2.7-fold) and lungs sections of mutant mice

• in contrast, OVA-sensitized homozygotes exhibit normal numbers of inflammatory cells in BAL and lung sections with no differences in eosinophilia or cytokine production by OVA-stimulated splenocytes relative to wild-type controls in T_H2-polarizing conditions (GM-CSF alone), indicating that T_H2-mediated lung inflammation is normal

hematopoietic system

increased T cell proliferation ( J:84973 )

• in MLR experiments, mutant irradiated B lymphoblasts (H-2^b/b) show a 2-fold increase in their capacity to stimulate alloreactive T cells (both CD4 and CD8 populations) derived from BALB/c mice (H-2^d/d) relative to wild-type B lymphoblasts

abnormal T-helper 1 physiology ( J:84973 )

• homozygotes develop more severe T helper 1 (T_H1)-mediated lung inflammation than wild-type controls

• in contrast, T_H2-mediated airway inflammation is similar to that in wild-type controls

cellular

increased T cell proliferation ( J:84973 )

• in MLR experiments, mutant irradiated B lymphoblasts (H-2^b/b) show a 2-fold increase in their capacity to stimulate alloreactive T cells (both CD4 and CD8 populations) derived from BALB/c mice (H-2^d/d) relative to wild-type B lymphoblasts