All Phenotypes Ccr5<tm1Kuz> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Ccr5^tm1Kuz/Ccr5^tm1Kuz	B6.129P2-Ccr5^tm1Kuz	MGI:4418655
hm2	Ccr5^tm1Kuz/Ccr5^tm1Kuz	B6.129P2-Ccr5^tm1Kuz/J	MGI:6460298
hm3	Ccr5^tm1Kuz/Ccr5^tm1Kuz	involves: 129P2/OlaHsd	MGI:5774773
hm4	Ccr5^tm1Kuz/Ccr5^tm1Kuz	involves: 129P2/OlaHsd * C57BL/6	MGI:3609170
ht5	Ccr5^tm1Kuz/Ccr5⁺	involves: 129P2/OlaHsd	MGI:5317841
cx6	Ccr5^tm1Kuz/Ccr5^tm1Kuz Cxcr4^tm1Qma/Cxcr4^tm1Qma	involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6	MGI:5317843
cx7	Ccr5^tm1Kuz/Ccr5^tm1Kuz Tg(CAG-EGFP)1Osb/?	involves: 129P2/OlaHsd * C3H * C57BL/6	MGI:5317844
cx8	Apoe^tm1Unc/Apoe^tm1Unc Ccr5^tm1Kuz/Ccr5^tm1Kuz	involves: 129P2/OlaHsd * C57BL/6	MGI:5317842

Allelic Composition	Ccr5^tm1Kuz/Ccr5^tm1Kuz
Genetic Background	B6.129P2-Ccr5^tm1Kuz

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ccr5^tm1Kuz mutation (2 available); any Ccr5 mutation (31 available)

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

respiratory system

bronchiolitis ( J:162707 )

• mice infected with a recombinant mouse-adapted SARS-CoV, rMA15, develop more severe denuding bronchiolitis than similarly infected wild-type mice

behavior/neurological

behavior/neurological phenotype ( J:84037 )

N	• response to kainic acid similar to controls • become catatonic and display staring behavior within 15 minutes • myoclonic twitching, frequent rearing and falling • seizures lasting up to 5 hours

abnormal conditioned taste aversion behavior ( J:102583 )

• female mice develop a stronger ethanol-induced conditioned taste aversion compared with similarly treated wild-type mice

increased fluid intake ( J:102583 )

• of an ethanol, saccharin, or quinine solution

increased alcohol consumption ( J:102583 )

• in female but not male mice

immune system

bronchiolitis ( J:162707 )

• mice infected with a recombinant mouse-adapted SARS-CoV, rMA15, develop more severe denuding bronchiolitis than similarly infected wild-type mice

increased susceptibility to Coronaviridae infection ( J:162707 )

• 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

mortality/aging

mortality/aging ( J:84037 )

N	• 40% mortality after kainic acid treatment

nervous system

nervous system phenotype ( J:84037 )

N	• selective CA3 hippocampal pycnosis after kainic acid treatment as in controls • susceptibility of cerebral granule cell neurons to kainic acid is similar to controls

vision/eye

cornea vascularization ( J:118018 )

• 34% less neovascularization than controls 2 weeks after denudation of corneal epithelium

• 34.9% less neovascularization than controls 4 weeks after denudation of corneal epithelium

cardiovascular system

cornea vascularization ( J:118018 )

• 34% less neovascularization than controls 2 weeks after denudation of corneal epithelium

• 34.9% less neovascularization than controls 4 weeks after denudation of corneal epithelium

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Coronavirus infectious disease		DOID:0080599		J:162707

Allelic Composition	Ccr5^tm1Kuz/Ccr5^tm1Kuz
Genetic Background	B6.129P2-Ccr5^tm1Kuz/J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ccr5^tm1Kuz mutation (2 available); any Ccr5 mutation (31 available)

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

behavior/neurological

impaired exercise endurance ( J:264446 )

• in a forced swimming test, mutant mice show a small but significant decrease in swimming time relative to wild-type controls

• administration of ORM1 fails to increase swimming time, unlike in wild-type controls, indicating that CCR5 mediates the anti-fatigue effect of ORM1

homeostasis/metabolism

impaired exercise endurance ( J:264446 )

• in a forced swimming test, mutant mice show a small but significant decrease in swimming time relative to wild-type controls

• administration of ORM1 fails to increase swimming time, unlike in wild-type controls, indicating that CCR5 mediates the anti-fatigue effect of ORM1

decreased skeletal muscle glycogen level ( J:264446 )

• mutant mice show a small but significant decrease in skeletal muscle glycogen content relative to wild-type controls

• administration of ORM1 fails to increase muscle glycogen content, unlike in wild-type controls

muscle

decreased skeletal muscle glycogen level ( J:264446 )

• mutant mice show a small but significant decrease in skeletal muscle glycogen content relative to wild-type controls

• administration of ORM1 fails to increase muscle glycogen content, unlike in wild-type controls

Allelic Composition	Ccr5^tm1Kuz/Ccr5^tm1Kuz
Genetic Background	involves: 129P2/OlaHsd

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ccr5^tm1Kuz mutation (2 available); any Ccr5 mutation (31 available)

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

homeostasis/metabolism

decreased susceptibility to injury ( J:227458 )

• 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

cardiovascular system

abnormal heart size ( J:227458 )

• after hypoxia exposure for 18 days, right ventricular hypertrophy is less severe in mutants than in wild-type mice

abnormal cardiovascular system physiology ( J:227458 )

• 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

decreased right ventricle systolic pressure ( J:227458 )

• after hypoxia exposure for 18 days, right ventricular systolic pressure is lower in mutants than in wild-type mice

immune system

decreased inflammatory response ( 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

• mice show lower counts of lung inflammatory monocytes than wild-type mice during both normoxia and hypoxia

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

immune system

abnormal Kupffer cell morphology ( J:152548 )

• infiltration of Kupffer cells an NK cells is strongly reduced after bile duct ligation

• mediates liver fibrosis primarily through resident liver cells

impaired macrophage chemotaxis ( J:64293 , J:84243 , J:153059 )

• 80% fewer macrophages compared to control in Ag-loaded gelatin sponge DTH assay (J:64293)

• delay in induced peritoneal macrophage accumulation, however, accumulation of neutrophils/eosinophils is unchanged (J:84243)

• reduced chemotaxis response (J:153059)

decreased susceptibility to induced colitis ( J:110814 )

• null mice show clinically less severe DSS-mediated colitis than wild-type or Ccr2-nulls

decreased NK cell number ( J:135308 )

• 4 fold reduction of tumor infiltrating NK cells when mice are injected with B16 melanoma cells

increased NK T cell number ( J:110814 )

• 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

abnormal CD4-positive, alpha beta T cell morphology ( J:110814 )

• intestinal mucosa shows enhanced infiltration of CD4+ lymphocytes by day 7 compared to wild-type or Ccr2-deficient mice

• mice have an increased number of CD4+ T cells before and during DSS-induced colitis

abnormal CD8-positive, alpha beta T cell morphology ( J:110814 )

abnormal NK T cell physiology ( J:100869 )

• increased resistance to activation induced cell death

• increased numbers of Il4 producing cells

• increased FasL expressing cells

decreased microglial cell activation ( J:153059 )

• significant reduction in activated microglia in the hippocampus 8 hours after injection of beta amyloid 1-40

abnormal cytokine level ( J:110814 )

• 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

increased susceptibility to fungal infection ( J:64293 )

• reduced survival following inoculation with Cryptococcus neoformans, 40% die by week 8 due to CNS infection (hydrocephalus)

• infected mice exhibit increased mononuclear cell recruitment to lungs, but not brain

• by week 5 infected mice exhibit cryptococcal meningitis cranial swelling, ruffled fur, staggered gait, lethargy and unresponsiveness, and decreased limb function

• brains of infected mice develop loss of neural tissue integrity , and large amounts of extracellelular cryptococcal polysaccharide capsule

decreased susceptibility to Retroviridae infection ( J:132342 )

• abrogated neurotoxicity to gp120 from a CCR5 preferring isolate of HIV

• abrogated neurotoxicity to gp120 from a CCR4 preferring isolate of HIV

behavior/neurological

abnormal spatial learning ( J:153059 )

• improved learning performance in a Morris water maze after injection of beta amyloid 1-40 relative to controls

abnormal long-term spatial reference memory ( J:153059 )

• in a Morris water maze

abnormal locomotor behavior ( J:110814 )

• mice show little reduction in activity with DSS treatment, unlike wild-type which become very lethargic with time

digestive/alimentary system

decreased susceptibility to induced colitis ( J:110814 )

• null mice show clinically less severe DSS-mediated colitis than wild-type or Ccr2-nulls

hematopoietic system

abnormal Kupffer cell morphology ( J:152548 )

• infiltration of Kupffer cells an NK cells is strongly reduced after bile duct ligation

• mediates liver fibrosis primarily through resident liver cells

impaired macrophage chemotaxis ( J:64293 , J:84243 , J:153059 )

• 80% fewer macrophages compared to control in Ag-loaded gelatin sponge DTH assay (J:64293)

• delay in induced peritoneal macrophage accumulation, however, accumulation of neutrophils/eosinophils is unchanged (J:84243)

• reduced chemotaxis response (J:153059)

decreased NK cell number ( J:135308 )

• 4 fold reduction of tumor infiltrating NK cells when mice are injected with B16 melanoma cells

increased NK T cell number ( J:110814 )

• 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

abnormal CD4-positive, alpha beta T cell morphology ( J:110814 )

• intestinal mucosa shows enhanced infiltration of CD4+ lymphocytes by day 7 compared to wild-type or Ccr2-deficient mice

• mice have an increased number of CD4+ T cells before and during DSS-induced colitis

abnormal CD8-positive, alpha beta T cell morphology ( J:110814 )

abnormal NK T cell physiology ( J:100869 )

• increased resistance to activation induced cell death

• increased numbers of Il4 producing cells

• increased FasL expressing cells

decreased microglial cell activation ( J:153059 )

• significant reduction in activated microglia in the hippocampus 8 hours after injection of beta amyloid 1-40

homeostasis/metabolism

abnormal cytokine level ( J:110814 )

• 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

cellular

impaired macrophage chemotaxis ( J:64293 , J:84243 , J:153059 )

• 80% fewer macrophages compared to control in Ag-loaded gelatin sponge DTH assay (J:64293)

• delay in induced peritoneal macrophage accumulation, however, accumulation of neutrophils/eosinophils is unchanged (J:84243)

• reduced chemotaxis response (J:153059)

nervous system

abnormal nervous system physiology ( J:132342 )

• abrogated neurotoxicity to gp120 from a CCR5 preferring isolate of HIV

• abrogated neurotoxicity to gp120 from a CCR4 preferring isolate of HIV

abnormal glial cell physiology ( J:153059 )

decreased microglial cell activation ( J:153059 )

• significant reduction in activated microglia in the hippocampus 8 hours after injection of beta amyloid 1-40

abnormal astrocyte physiology ( J:153059 )

• significant reduction in activated astrocytes in the hippocampus 6 hours after injection of beta amyloid 1-40

cardiovascular system

abnormal Kupffer cell morphology ( J:152548 )

• infiltration of Kupffer cells an NK cells is strongly reduced after bile duct ligation

• mediates liver fibrosis primarily through resident liver cells

liver/biliary system

abnormal Kupffer cell morphology ( J:152548 )

• infiltration of Kupffer cells an NK cells is strongly reduced after bile duct ligation

• mediates liver fibrosis primarily through resident liver cells

abnormal Ito cell morphology ( J:152548 )

• complete suppression of hepatic stellate cell migration

abnormal hepatocyte physiology ( J:100869 )

• injection of Concanavalin A results in 25% increase in damage

• hepatocellular necrosis

liver failure ( J:100869 )

• injection of Concanavalin A leads to fulminant liver failure and 50% mortality within 8 hours whereas all controls survive

• antibody depletion of NKT cells improves liver damage

• IL4 depletion improves liver damage

Allelic Composition	Ccr5^tm1Kuz/Ccr5⁺
Genetic Background	involves: 129P2/OlaHsd

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ccr5^tm1Kuz mutation (2 available); any Ccr5 mutation (31 available)

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

reproductive system

reproductive system phenotype ( J:119074 )

N	• normal pregnancies

Allelic Composition	Ccr5^tm1Kuz/Ccr5^tm1Kuz Cxcr4^tm1Qma/Cxcr4^tm1Qma
Genetic Background	involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ccr5^tm1Kuz mutation (2 available); any Ccr5 mutation (31 available)
Cxcr4^tm1Qma mutation (1 available); any Cxcr4 mutation (46 available)

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

nervous system

abnormal nervous system physiology ( J:132342 )

• abrogated neurotoxicity to gp120 from a CCR5 preferring isolate of HIV

• abrogated neurotoxicity to gp120 from a CCR4 preferring isolate of HIV

immune system

decreased susceptibility to Retroviridae infection ( J:132342 )

• abrogated neurotoxicity to gp120 from a CCR5 preferring isolate of HIV

• abrogated neurotoxicity to gp120 from a CCR4 preferring isolate of HIV

Allelic Composition	Ccr5^tm1Kuz/Ccr5^tm1Kuz Tg(CAG-EGFP)1Osb/?
Genetic Background	involves: 129P2/OlaHsd * C3H * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ccr5^tm1Kuz mutation (2 available); any Ccr5 mutation (31 available)
Tg(CAG-EGFP)1Osb mutation (8 available)

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

neoplasm

decreased metastatic potential ( J:97833 )

• 40.2 metastic colonies compared to 70.6 colonies for controls 14 days after injecting B16-F10 melanoma cells

• fewer metastatic tumors 14 days after injecting irradiated mice with melanoma cells

• injection of wild type lung stromal cells enhanced metastasis relative to injection of mutant stromal cells

• improved survival

Allelic Composition	Apoe^tm1Unc/Apoe^tm1Unc Ccr5^tm1Kuz/Ccr5^tm1Kuz
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Apoe^tm1Unc mutation (33 available); any Apoe mutation (158 available)
Ccr5^tm1Kuz mutation (2 available); any Ccr5 mutation (31 available)

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

cardiovascular system

atherosclerotic lesions ( J:128063 )

• reduced plaque areas after 10-12 weeks on a high fat or high cholesterol diet

• both in the aortic root and the thoracoabdominal artery

• also at 22 weeks when fed a normal diet

abnormal vascular smooth muscle morphology ( J:128063 )

• increased smooth muscle content in atherosclerotic plaques

immune system

decreased T cell number ( J:128063 )

• in atherosclerotic plaques reduced 24% compared to Apoe^tm1Unc

abnormal mononuclear phagocyte morphology ( J:128063 )

• monocyte/macrophage in atherosclerotic plaques reduced 77% compared to Apoe^tm1Unc

abnormal lymphocyte physiology ( J:128063 )

• reduced proliferative responses of splenocytes and of lymph node cells by 25% compared to Apoe^tm1Unc

abnormal cytokine secretion ( J:128063 )

decreased interferon-gamma secretion ( J:128063 )

• significantly decreased secretion by splenocytes

increased interleukin-10 secretion ( J:128063 )

• increased content in atherosclerotic plaques

• increased secretion by both splenocytes and by lymph node cells

muscle

abnormal vascular smooth muscle morphology ( J:128063 )

• increased smooth muscle content in atherosclerotic plaques

hematopoietic system

decreased T cell number ( J:128063 )

• in atherosclerotic plaques reduced 24% compared to Apoe^tm1Unc

abnormal mononuclear phagocyte morphology ( J:128063 )

• monocyte/macrophage in atherosclerotic plaques reduced 77% compared to Apoe^tm1Unc

abnormal lymphocyte physiology ( J:128063 )

• reduced proliferative responses of splenocytes and of lymph node cells by 25% compared to Apoe^tm1Unc

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