behavior/neurological phenotype

• abnormal locomotor behavior
  • mice show little reduction in activity with DSS treatment, unlike wild-type which become very lethargic with time
  (MGI Ref ID J:110814)

• abnormal spatial learning
  • improved learning performance in a Morris water maze after injection of beta amyloid 1-40 relative to controls
  (MGI Ref ID J:153059)

• abnormal long term spatial reference memory
  • in a Morris water maze
  (MGI Ref ID J:153059)

hematopoietic system phenotype

• abnormal CD8-positive, alpha beta T cell morphology
  (MGI Ref ID J:110814)

• abnormal CD4-positive, alpha beta T cell morphology
  • intestinal mucosa shows enhanced infiltration of CD4+ lymphocytes by day 7 compared to wild-type or Ccr2-deficient mice
  (MGI Ref ID J:110814)
  • mice have an increased number of CD4+ T cells before and during DSS-induced colitis
  (MGI Ref ID J:110814)

• abnormal NK T cell physiology
  • increased numbers of Il4 producing cells
  (MGI Ref ID J:100869)
  • increased FasL expressing cells
  (MGI Ref ID J:100869)
  • increased resistance to activation induced cell death
  (MGI Ref ID J:100869)

• decreased microglial cell activation
  • significant reduction in activated microglia in the hippocampus 8 hours after injection of beta amyloid 1-40
  (MGI Ref ID J:153059)

• impaired macrophage chemotaxis
  • 80% fewer macrophages compared to control in Ag-loaded gelatin sponge DTH assay
  (MGI Ref ID J:64293)
  • reduced chemotaxis response
  (MGI Ref ID J:153059)
  • delay in induced peritoneal macrophage accumulation, however, accumulation of neutrophils/eosinophils is unchanged
  (MGI Ref ID J:84243)

• increased NK T cell number
  • null mice show a significant increase in NK 1.1+ T cells by day 3 and 7 of DSS-treatment; wild-type and Ccr2-null mice do not show as large of an increase
  (MGI Ref ID J:110814)

• abnormal Kupffer cell morphology
  • infiltration of Kupffer cells an NK cells is strongly reduced after bile duct ligation
  (MGI Ref ID J:152548)
  • mediates liver fibrosis primarily through resident liver cells
  (MGI Ref ID J:152548)

• decreased NK cell number
  • 4 fold reduction of tumor infiltrating NK cells when mice are injected with B16 melanoma cells
  (MGI Ref ID J:135308)

homeostasis/metabolism phenotype

• abnormal cytokine level
  • mice expression one fifth the wild-type level of Ifng after day 3 and 7, while Il-4 is increased 75-fold and a 2-fold increase in Il-5 and -10 over wild-type
  (MGI Ref ID J:110814)

immune system phenotype

• increased susceptibility to fungal infection
  • brains of infected mice develop loss of neural tissue integrity , and large amounts of extracellelular cryptococcal polysaccharide capsule
  (MGI Ref ID J:64293)
  • by week 5 infected mice exhibit cryptococcal meningitis ¿ cranial swelling, ruffled fur, staggered gait, lethargy and unresponsiveness, and decreased limb function
  (MGI Ref ID J:64293)
  • reduced survival following inoculation with Cryptococcus neoformans, 40% die by week 8 due to CNS infection (hydrocephalus)
  (MGI Ref ID J:64293)
  • infected mice exhibit increased mononuclear cell recruitment to lungs, but not brain
  (MGI Ref ID J:64293)

• abnormal NK T cell physiology
  • increased FasL expressing cells
  (MGI Ref ID J:100869)
  • increased numbers of Il4 producing cells
  (MGI Ref ID J:100869)
  • increased resistance to activation induced cell death
  (MGI Ref ID J:100869)

• decreased susceptibility to induced colitis
  • null mice show clinically less severe DSS-mediated colitis than wild-type or Ccr2-nulls
  (MGI Ref ID J:110814)

• impaired macrophage chemotaxis
  • reduced chemotaxis response
  (MGI Ref ID J:153059)
  • 80% fewer macrophages compared to control in Ag-loaded gelatin sponge DTH assay
  (MGI Ref ID J:64293)
  • delay in induced peritoneal macrophage accumulation, however, accumulation of neutrophils/eosinophils is unchanged
  (MGI Ref ID J:84243)

• increased NK T cell number
  • null mice show a significant increase in NK 1.1+ T cells by day 3 and 7 of DSS-treatment; wild-type and Ccr2-null mice do not show as large of an increase
  (MGI Ref ID J:110814)

• abnormal cytokine level
  • mice expression one fifth the wild-type level of Ifng after day 3 and 7, while Il-4 is increased 75-fold and a 2-fold increase in Il-5 and -10 over wild-type
  (MGI Ref ID J:110814)

• decreased susceptibility to Retroviridae infection
  • abrogated neurotoxicity to gp120 from a CCR5 preferring isolate of HIV
  (MGI Ref ID J:132342)
  • abrogated neurotoxicity to gp120 from a CCR4 preferring isolate of HIV
  (MGI Ref ID J:132342)

• decreased NK cell number
  • 4 fold reduction of tumor infiltrating NK cells when mice are injected with B16 melanoma cells
  (MGI Ref ID J:135308)

• decreased susceptibility to viral infection
  • abrogated neurotoxicity to gp120 from a CCR4 preferring isolate of HIV
  (MGI Ref ID J:132342)
  • abrogated neurotoxicity to gp120 from a CCR5 preferring isolate of HIV
  (MGI Ref ID J:132342)

• abnormal CD8-positive, alpha beta T cell morphology
  (MGI Ref ID J:110814)

• decreased microglial cell activation
  • significant reduction in activated microglia in the hippocampus 8 hours after injection of beta amyloid 1-40
  (MGI Ref ID J:153059)

• abnormal CD4-positive, alpha beta T cell morphology
  • intestinal mucosa shows enhanced infiltration of CD4+ lymphocytes by day 7 compared to wild-type or Ccr2-deficient mice
  (MGI Ref ID J:110814)
  • mice have an increased number of CD4+ T cells before and during DSS-induced colitis
  (MGI Ref ID J:110814)

• abnormal Kupffer cell morphology
  • infiltration of Kupffer cells an NK cells is strongly reduced after bile duct ligation
  (MGI Ref ID J:152548)
  • mediates liver fibrosis primarily through resident liver cells
  (MGI Ref ID J:152548)

cardiovascular system phenotype

• abnormal Kupffer cell morphology
  • mediates liver fibrosis primarily through resident liver cells
  (MGI Ref ID J:152548)
  • infiltration of Kupffer cells an NK cells is strongly reduced after bile duct ligation
  (MGI Ref ID J:152548)

liver/biliary system phenotype

• liver failure
  • antibody depletion of NKT cells improves liver damage
  (MGI Ref ID J:100869)
  • IL4 depletion improves liver damage
  (MGI Ref ID J:100869)
  • injection of Concanavalin A leads to fulminant liver failure and 50% mortality within 8 hours whereas all controls survive
  (MGI Ref ID J:100869)

• abnormal Ito cell morphology
  • complete suppression of hepatic stellate cell migration
  (MGI Ref ID J:152548)

• abnormal Kupffer cell morphology
  • mediates liver fibrosis primarily through resident liver cells
  (MGI Ref ID J:152548)
  • infiltration of Kupffer cells an NK cells is strongly reduced after bile duct ligation
  (MGI Ref ID J:152548)

• abnormal hepatocyte physiology
  • hepatocellular necrosis
  (MGI Ref ID J:100869)
  • injection of Concanavalin A results in 25% increase in damage
  (MGI Ref ID J:100869)

nervous system phenotype

• decreased microglial cell activation
  • significant reduction in activated microglia in the hippocampus 8 hours after injection of beta amyloid 1-40
  (MGI Ref ID J:153059)

• abnormal nervous system physiology
  • abrogated neurotoxicity to gp120 from a CCR5 preferring isolate of HIV
  (MGI Ref ID J:132342)
  • abrogated neurotoxicity to gp120 from a CCR4 preferring isolate of HIV
  (MGI Ref ID J:132342)

• abnormal astrocyte physiology
  • significant reduction in activated astrocytes in the hippocampus 6 hours after injection of beta amyloid 1-40
  (MGI Ref ID J:153059)

• abnormal glial cell physiology
  (MGI Ref ID J:153059)

cellular phenotype

• impaired macrophage chemotaxis
  • reduced chemotaxis response
  (MGI Ref ID J:153059)
  • delay in induced peritoneal macrophage accumulation, however, accumulation of neutrophils/eosinophils is unchanged
  (MGI Ref ID J:84243)
  • 80% fewer macrophages compared to control in Ag-loaded gelatin sponge DTH assay
  (MGI Ref ID J:64293)

digestive/alimentary phenotype

• decreased susceptibility to induced colitis
  • null mice show clinically less severe DSS-mediated colitis than wild-type or Ccr2-nulls
  (MGI Ref ID J:110814)

cardiovascular system phenotype

• abnormal heart size
  • after hypoxia exposure for 18 days, right ventricular hypertrophy is less severe in mutants than in wild-type mice
  (MGI Ref ID J:227458)

• abnormal cardiovascular system physiology
  • after hypoxia exposure for 18 days, distal pulmonary vessels exhibit less muscularization than wild-type mice, with a smaller percentage of dividing Ki67-positive pulmonary vascular cells
  (MGI Ref ID J:227458)

• decreased right ventricle systolic pressure
  • after hypoxia exposure for 18 days, right ventricular systolic pressure is lower in mutants than in wild-type mice
  (MGI Ref ID J:227458)

homeostasis/metabolism phenotype

• decreased susceptibility to injury
  • after hypoxia exposure for 18 days, mice show lower right ventricular systolic pressure, less severe right ventricular hypertrophy, less muscularization of the distal pulmonary vessels with a smaller percentage of dividing Ki67-positive pulmonary vascular cells, lower counts of lung inflammatory monocytes and lower number of macrophages surrounding pulmonary vessels or present in the BAL fluid
  (MGI Ref ID J:227458)

immune system phenotype

• decreased inflammatory response
  • mice show lower counts of lung inflammatory monocytes than wild-type mice during both normoxia and hypoxia
  (MGI Ref ID J:227458)
  • the number of macrophages surrounding pulmonary vessels or present in BAL fluid is not increased from normoxia to hypoxia as is seen in wild-type mice
  (MGI Ref ID J:227458)

respiratory system phenotype

• bronchiolitis
  • mice infected with a recombinant mouse-adapted SARS-CoV, rMA15, develop more severe denuding bronchiolitis than similarly infected wild-type mice
  (MGI Ref ID J:162707)

vision/eye phenotype

• corneal vascularization
  • 34.9% less neovascularization than controls 4 weeks after denudation of corneal epithelium
  (MGI Ref ID J:118018)
  • 34% less neovascularization than controls 2 weeks after denudation of corneal epithelium
  (MGI Ref ID J:118018)

behavior/neurological phenotype

• increased fluid intake
  • of an ethanol, saccharin, or quinine solution
  (MGI Ref ID J:102583)

• abnormal conditioned taste aversion behavior
  • female mice develop a stronger ethanol-induced conditioned taste aversion compared with similarly treated wild-type mice
  (MGI Ref ID J:102583)

• increased alcohol consumption
  • in female but not male mice
  (MGI Ref ID J:102583)

cardiovascular system phenotype

• corneal vascularization
  • 34% less neovascularization than controls 2 weeks after denudation of corneal epithelium
  (MGI Ref ID J:118018)
  • 34.9% less neovascularization than controls 4 weeks after denudation of corneal epithelium
  (MGI Ref ID J:118018)

immune system phenotype

• bronchiolitis
  • mice infected with a recombinant mouse-adapted SARS-CoV, rMA15, develop more severe denuding bronchiolitis than similarly infected wild-type mice
  (MGI Ref ID J:162707)

• increased susceptibility to viral infection
  • mice show increased susceptibility to infection with a recombinant mouse-adapted SARS-CoV, rMA15, developing more severe and prolonged disease compared to wild-type mice, showing more prominent airway epithelial cell apoptosis, severe denuding bronchiolitis and perivenular/periarterial cuffing
  (MGI Ref ID J:162707)

• increased susceptibility to Coronaviridae infection
  • mice show increased susceptibility to infection with a recombinant mouse-adapted SARS-CoV, rMA15 , developing more severe and prolonged disease compared to wild-type mice, showing more prominent airway epithelial cell apoptosis, severe denuding bronchiolitis and perivenular/periarterial cuffing
  (MGI Ref ID J:162707)

mammalian phenotype

• behavior/neurological phenotype
  • Normal - become catatonic and display staring behavior within 15 minutes
  (MGI Ref ID J:84037)
  • Normal - response to kainic acid similar to controls
  (MGI Ref ID J:84037)
  • Normal - seizures lasting up to 5 hours
  (MGI Ref ID J:84037)
  • Normal - myoclonic twitching, frequent rearing and falling
  (MGI Ref ID J:84037)

• nervous system phenotype
  • Normal - susceptibility of cerebral granule cell neurons to kainic acid is similar to controls
  (MGI Ref ID J:84037)
  • Normal - selective CA3 hippocampal pycnosis after kainic acid treatment as in controls
  (MGI Ref ID J:84037)

• mortality/aging
  • Normal - 40% mortality after kainic acid treatment
  (MGI Ref ID J:84037)

behavior/neurological phenotype

• impaired exercise endurance
  • in a forced swimming test, mutant mice show a small but significant decrease in swimming time relative to wild-type controls
  (MGI Ref ID J:264446)
  • administration of ORM1 fails to increase swimming time, unlike in wild-type controls, indicating that CCR5 mediates the anti-fatigue effect of ORM1
  (MGI Ref ID J:264446)

homeostasis/metabolism phenotype

• decreased skeletal muscle glycogen level
  • mutant mice show a small but significant decrease in skeletal muscle glycogen content relative to wild-type controls
  (MGI Ref ID J:264446)
  • administration of ORM1 fails to increase muscle glycogen content, unlike in wild-type controls
  (MGI Ref ID J:264446)

• impaired exercise endurance
  • in a forced swimming test, mutant mice show a small but significant decrease in swimming time relative to wild-type controls
  (MGI Ref ID J:264446)
  • administration of ORM1 fails to increase swimming time, unlike in wild-type controls, indicating that CCR5 mediates the anti-fatigue effect of ORM1
  (MGI Ref ID J:264446)

muscle phenotype

• decreased skeletal muscle glycogen level
  • administration of ORM1 fails to increase muscle glycogen content, unlike in wild-type controls
  (MGI Ref ID J:264446)
  • mutant mice show a small but significant decrease in skeletal muscle glycogen content relative to wild-type controls
  (MGI Ref ID J:264446)