Phenotypes associated with this allele

• Allele Symbol: C3ar1^tm1Raw
• Allele Name: targeted mutation 1, Rick A Wetsel
• Allele ID: MGI:2158707
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	C3ar1^tm1Raw/C3ar1^tm1Raw	B6.129X1(B6)-C3ar1^tm1Raw	MGI:3606656
hm2	C3ar1^tm1Raw/C3ar1^tm1Raw	involves: 129X1/SvJ * C57BL/6	MGI:2449074
ht3	C3ar1^tm1Raw/C3ar1^+	involves: 129X1/SvJ * C57BL/6	MGI:2449075
cx4	C3ar1^tm1Raw/C3ar1^tm1Raw Cpn1^tm1Raw/Cpn1^tm1Raw	B6.129-C3ar1^tm1Raw Cpn1^tm1Raw	MGI:3844645

Genotype
MGI:3606656

hm1

• Allelic Composition: C3ar1^tm1Raw/C3ar1^tm1Raw
• Genetic Background: B6.129X1(B6)-C3ar1^tm1Raw

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

immune system

abnormal T-helper 2 cell differentiation ( J:80071 )

• homozygotes display abnormal Th2 development in a pulmonary allergy model

decreased eosinophil cell number ( J:80071 )

• in the A. fumigatus/OVA model of pulmonary allergy, Ag-challenged homozygotes show an 88% reduction in airway eosinophils relative to wild-type mice

decreased neutrophil cell number ( J:80071 )

• in the A. fumigatus/OVA model of pulmonary allergy, Ag-challenged homozygotes show an 79% reduction in airway neutrophils relative to wild-type mice

decreased lymphocyte cell number ( J:80071 )

• in the A. fumigatus/OVA model of pulmonary allergy, Ag-challenged homozygotes show an 54% reduction in airway lymphocytes relative to wild-type mice

abnormal interleukin level ( J:80071 )

• consistent with a reduction in IL-4-producing cells, Ag-challenged homozygotes show reduced bronchoalveolar lavage levels of Th2 cytokines, IL-5 and IL-13

increased circulating interleukin-1 beta level ( J:93791 )

• homozygotes with MOG-induced EAE exhibit an >10-fold increase in IL-1beta mRNA levels; however, no corresponding increase in IL-1beta protein levels (or several other cytokines) is noted in mutant spinal cords

abnormal adaptive immunity ( J:80071 )

• homozygotes exhibit an abrogated adaptive Th2 immune response in an experimental allergic asthma model

abnormal eosinophil physiology ( J:80071 )

• in the A. fumigatus/OVA model of pulmonary allergy, Ag-challenged homozygotes exhibit reduced eosinophil recruitment into the peribronchial region between pulmonary blood vessels and the airways

impaired neutrophil recruitment ( J:80071 )

• in the A. fumigatus/OVA model of pulmonary allergy, Ag-challenged homozygotes exhibit reduced lung neutrophil recruitment

decreased IgE level ( J:80071 )

• in the A. fumigatus/OVA model of pulmonary allergy, Ag-challenged homozygotes show a 40% reduction in total IgE levels relative to wild-type mice; Ag-specific IgE levels are decreased by 70%

decreased IgG1 level ( J:80071 )

• in the A. fumigatus/OVA model of pulmonary allergy, Ag-challenged homozygotes show a 64% reduction in Ag-specific IgG1 levels relative to wild-type mice

abnormal T-helper 2 physiology ( J:80071 )

• in the A. fumigatus/OVA model of pulmonary allergy, Ag-challenged homozygotes display an impaired Th2 immune response, i.e. severely reduced Th2 activation and recruitment to lung

increased susceptibility to type I hypersensitivity reaction ( J:80071 )

• in the A. fumigatus/OVA model of pulmonary allergy, Ag-challenged homozygotes display an attenuated allergic (asthma-like) response relative to wild-type mice

decreased interleukin-4 secretion ( J:80071 )

• in the A. fumigatus/OVA model of pulmonary allergy, Ag-challenged homozygotes show a 59% reduction in lung IL-4-producing cells relative to wild-type mice

decreased susceptibility to experimental autoimmune encephalomyelitis ( J:93791 )

• homozygotes exhibit attenuated disease severity in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), with a lower cumulative disease index relative to wild-type mice (48.2 vs 66.7)

• however, upon in vitro stimulation with MOG_35-55 peptide, mutant splenic T cells exhibit normal proliferative (i.e. encephalitogenic-inducing) capacity

hematopoietic system

abnormal T-helper 2 cell differentiation ( J:80071 )

• homozygotes display abnormal Th2 development in a pulmonary allergy model

decreased eosinophil cell number ( J:80071 )

• in the A. fumigatus/OVA model of pulmonary allergy, Ag-challenged homozygotes show an 88% reduction in airway eosinophils relative to wild-type mice

decreased neutrophil cell number ( J:80071 )

• in the A. fumigatus/OVA model of pulmonary allergy, Ag-challenged homozygotes show an 79% reduction in airway neutrophils relative to wild-type mice

decreased lymphocyte cell number ( J:80071 )

• in the A. fumigatus/OVA model of pulmonary allergy, Ag-challenged homozygotes show an 54% reduction in airway lymphocytes relative to wild-type mice

abnormal eosinophil physiology ( J:80071 )

• in the A. fumigatus/OVA model of pulmonary allergy, Ag-challenged homozygotes exhibit reduced eosinophil recruitment into the peribronchial region between pulmonary blood vessels and the airways

impaired neutrophil recruitment ( J:80071 )

• in the A. fumigatus/OVA model of pulmonary allergy, Ag-challenged homozygotes exhibit reduced lung neutrophil recruitment

decreased IgE level ( J:80071 )

• in the A. fumigatus/OVA model of pulmonary allergy, Ag-challenged homozygotes show a 40% reduction in total IgE levels relative to wild-type mice; Ag-specific IgE levels are decreased by 70%

decreased IgG1 level ( J:80071 )

• in the A. fumigatus/OVA model of pulmonary allergy, Ag-challenged homozygotes show a 64% reduction in Ag-specific IgG1 levels relative to wild-type mice

abnormal T-helper 2 physiology ( J:80071 )

• in the A. fumigatus/OVA model of pulmonary allergy, Ag-challenged homozygotes display an impaired Th2 immune response, i.e. severely reduced Th2 activation and recruitment to lung

respiratory system

abnormal respiratory mucosa goblet cell morphology ( J:80071 )

• in the A. fumigatus/OVA model of pulmonary allergy, Ag-challenged homozygotes show a 52% reduction in bronchoalveolar lavage mucin levels relative to wild-type mice

decreased airway responsiveness ( J:80071 )

• in the A. fumigatus/OVA model of pulmonary allergy, Ag-challenged homozygotes exhibit a significantly attenuated airway responsiveness, as shown by decreased sensitivity to i.v. acetylcholine (ACh) challenge

liver/biliary system

impaired liver regeneration ( J:91917 )

• at 14-16 weeks, female homozygotes exhibit impaired liver regeneration, as shown by a reduced number of BrdU-positive hepatocyte nuclei at 48 hrs after CCl₄-induced toxic liver injury

nervous system

demyelination ( J:93791 )

• when subjected to MOG-induced EAE, homozygotes exhibit a mild reduction in cellular infiltration and demyelination in the spinal cord relative to wild-type mice

homeostasis/metabolism

abnormal interleukin level ( J:80071 )

• consistent with a reduction in IL-4-producing cells, Ag-challenged homozygotes show reduced bronchoalveolar lavage levels of Th2 cytokines, IL-5 and IL-13

increased circulating interleukin-1 beta level ( J:93791 )

• homozygotes with MOG-induced EAE exhibit an >10-fold increase in IL-1beta mRNA levels; however, no corresponding increase in IL-1beta protein levels (or several other cytokines) is noted in mutant spinal cords

Genotype
MGI:2449074

hm2

• Allelic Composition: C3ar1^tm1Raw/C3ar1^tm1Raw
• Genetic Background: involves: 129X1/SvJ * C57BL/6

mortality/aging

mortality/aging ( J:68807 )

N • homozygotes are viable and fertile and exhibit normal size, behavior, and histology in major organ systems (including brain, kidney, liver, lungs, testis, ovaries, heart, intestine, adrenal, and thymus)

increased susceptibility to induced morbidity/mortality ( J:68807 )

• at 6-10 weeks, homozygotes are more sensitive to LPS-induced lethality; at 48 mg/kg, 85% of homozygotes die within 3 days, compared with only 17% of wild-type mice

immune system

increased circulating interleukin-1 beta level ( J:68807 )

• after LPS challenge, homozygotes exhibit a 3-fold increase in plasma IL-1beta levels relative to wild-type mice

• after LPS challenge, homozygotes exhibit increased plasma levels of proinflammatory cytokines IL-1beta, IL-6, and TNF relative to wild-type mice; however, only changes in IL-1beta levels are statistically significant

• no significant differences are observed in plasma IL-10 levels or nitrite/nitrate levels after LPS challenge

increased susceptibility to endotoxin shock ( J:68807 )

• when subjected to an endotoxin-induced model of sepsis, homozygotes display increased sensitivity to LPS-induced shock relative to wild-type mice

hematopoietic system

hematopoietic system phenotype ( J:68807 )

N • homozygotes exhibit normal hematology profiles relative to wild-type mice

homeostasis/metabolism

increased circulating interleukin-1 beta level ( J:68807 )

• after LPS challenge, homozygotes exhibit a 3-fold increase in plasma IL-1beta levels relative to wild-type mice

• after LPS challenge, homozygotes exhibit increased plasma levels of proinflammatory cytokines IL-1beta, IL-6, and TNF relative to wild-type mice; however, only changes in IL-1beta levels are statistically significant

• no significant differences are observed in plasma IL-10 levels or nitrite/nitrate levels after LPS challenge

Genotype
MGI:2449075

ht3

• Allelic Composition: C3ar1^tm1Raw/C3ar1⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:68807 )

• heterozygotes more sensitive to to LPS-induced lethality than wild-type mice, but less sensitive than homozygotes, indicating a gene dosage effect

immune system

abnormal immune system physiology ( J:68807 )

• when subjected to an endotoxin-induced model of sepsis, heterozygotes display an intermediate sensitivity to LPS-induced shock

Genotype
MGI:3844645

cx4

• Allelic Composition: C3ar1^tm1Raw/C3ar1^tm1Raw; Cpn1^tm1Raw/Cpn1^tm1Raw
• Genetic Background: B6.129-C3ar1^tm1Raw Cpn1^tm1Raw

immune system

increased acute inflammation ( J:148315 )

• more mice die than controls when administered complement-activating cobra venom (6 of 18 vs. 2 of 16 wild-type mice)