Overview

Also Known As:CCR5 KO

Absence of chemokine (C-C motif) receptor 5 in these knock-out mice affects immune and a number of other physiological responses. They are useful for widespread studies of innate immunity.

Donating Investigator

Israel F. Charo, Gladstone Inst of Cardiovascular Disease, UCSF

Genetic overview

Genetic Background	Generation
	N12+F4 (2019-07-11 00:00:00)

Ccr5^tm1Kuz

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Ccr5	chemokine (C-C motif) receptor 5

View Genetics

Research Applications

Immunology, Inflammation and Autoimmunity Research
Cancer Research

View All Research Applications

Base Price

Starting at:

$236.78 Domestic price for female 4-week

View Price List

Details

Detailed Description

At birth, mice homozygous for the targeted allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No transcript is detected in splenocytes or peritoneal macrophages. Thioglycollate-elicited peritoneal macrophages from homozygotes exhibit a delayed period before reaching peak mobilization (72 hours vs. 36 for wild type mice).

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain 5427. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector containing a neomycin resistance gene was used to disrupt the single coding exon of the targeted gene. The construct was electroporated into 129P2/OlaHsd-derived E14TG2A embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts to obtain chimeric animals. Mutant mice were maintained on a mixed C57BL/6 and 129P2 background for a period of time before they were donated to the Jackson Laboratory Induced Mutant Resource (IMR) by Dr. William Kuziel. Subsequently they were obtained by Dr. Israel Charo (Gladstone Institute of Cardiovascular Disease, UCSF) and backcrossed to C57BL/6 ten times before being imported once more into the IMR. The mice were crossed to C57BL/6J once upon arrival.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Kuziel WA; Dawson TC; Quinones M; Garavito E; Chenaux G; Ahuja SS; Reddick RL; Maeda N. 2003. CCR5 deficiency is not protective in the early stages of atherogenesis in apoE knockout mice. Atherosclerosis 167(1):25-32PubMed: 12618265 MGI: J:84243

View All References

Genetics

Ccr5^tm1Kuz

Allele Symbol: Ccr5^tm1Kuz

Allele Name	targeted mutation 1, William A Kuziel
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	CCR5-; CCR5 KO; Cmkbr5^tm1Kuz
Gene Symbol and Name	Ccr5, chemokine (C-C motif) receptor 5
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	9
Molecular Note	The exon containing the entire coding region was replaced with a neomycin resistance gene inserted by homologous recombination.
Mutations Made By	Dr. William Kuziel, Protein Design Laboratories

Disease/Phenotype

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Ccr5^tm1Kuz related

Immunology, Inflammation and Autoimmunity Research
- Growth Factors/Receptors/Cytokines
Cancer Research
- Growth Factors/Receptors/Cytokines

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Ccr5^tm1Kuz/Ccr5^tm1Kuz
involves: 129P2/OlaHsd * C57BL/6

behavior/neurological phenotype

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

abnormal long term spatial reference memory
- in a Morris water maze

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

hematopoietic system phenotype

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

abnormal CD8-positive, alpha beta T cell morphology

abnormal Kupffer cell morphology
- infiltration of Kupffer cells an NK cells is strongly reduced after bile duct ligation
- mediates liver fibrosis primarily through resident liver cells

abnormal NK T cell physiology
- increased FasL expressing cells
- increased numbers of Il4 producing cells
- increased resistance to activation induced cell death

decreased microglial cell activation
- significant reduction in activated microglia in the hippocampus 8 hours after injection of beta amyloid 1-40

decreased NK cell number
- 4 fold reduction of tumor infiltrating NK cells when mice are injected with B16 melanoma cells

impaired macrophage chemotaxis
- 80% fewer macrophages compared to control in Ag-loaded gelatin sponge DTH assay
- delay in induced peritoneal macrophage accumulation, however, accumulation of neutrophils/eosinophils is unchanged
- reduced chemotaxis response

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

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

immune system phenotype

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

abnormal CD8-positive, alpha beta T cell morphology

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

abnormal Kupffer cell morphology
- infiltration of Kupffer cells an NK cells is strongly reduced after bile duct ligation
- mediates liver fibrosis primarily through resident liver cells

abnormal NK T cell physiology
- increased FasL expressing cells
- increased numbers of Il4 producing cells
- increased resistance to activation induced cell death

decreased microglial cell activation
- significant reduction in activated microglia in the hippocampus 8 hours after injection of beta amyloid 1-40

decreased NK cell number
- 4 fold reduction of tumor infiltrating NK cells when mice are injected with B16 melanoma cells

decreased susceptibility to induced colitis
- null mice show clinically less severe DSS-mediated colitis than wild-type or Ccr2-nulls

decreased susceptibility to Retroviridae infection
- abrogated neurotoxicity to gp120 from a CCR4 preferring isolate of HIV
- abrogated neurotoxicity to gp120 from a CCR5 preferring isolate of HIV

decreased susceptibility to viral infection
- abrogated neurotoxicity to gp120 from a CCR4 preferring isolate of HIV
- abrogated neurotoxicity to gp120 from a CCR5 preferring isolate of HIV

impaired macrophage chemotaxis
- 80% fewer macrophages compared to control in Ag-loaded gelatin sponge DTH assay
- delay in induced peritoneal macrophage accumulation, however, accumulation of neutrophils/eosinophils is unchanged
- reduced chemotaxis response

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

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

cardiovascular system phenotype

abnormal Kupffer cell morphology
- 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 phenotype

abnormal hepatocyte physiology
- hepatocellular necrosis
- injection of Concanavalin A results in 25% increase in damage

abnormal Ito cell morphology
- complete suppression of hepatic stellate cell migration

abnormal Kupffer cell morphology
- infiltration of Kupffer cells an NK cells is strongly reduced after bile duct ligation
- mediates liver fibrosis primarily through resident liver cells

liver failure
- antibody depletion of NKT cells improves liver damage
- IL4 depletion improves liver damage
- injection of Concanavalin A leads to fulminant liver failure and 50% mortality within 8 hours whereas all controls survive

nervous system phenotype

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

abnormal glial cell physiology

abnormal nervous system physiology
- abrogated neurotoxicity to gp120 from a CCR4 preferring isolate of HIV
- abrogated neurotoxicity to gp120 from a CCR5 preferring isolate of HIV

decreased microglial cell activation
- significant reduction in activated microglia in the hippocampus 8 hours after injection of beta amyloid 1-40

cellular phenotype

impaired macrophage chemotaxis
- 80% fewer macrophages compared to control in Ag-loaded gelatin sponge DTH assay
- delay in induced peritoneal macrophage accumulation, however, accumulation of neutrophils/eosinophils is unchanged
- reduced chemotaxis response

digestive/alimentary phenotype

decreased susceptibility to induced colitis
- null mice show clinically less severe DSS-mediated colitis than wild-type or Ccr2-nulls

Genotype: Ccr5^tm1Kuz/Ccr5^tm1Kuz
involves: 129P2/OlaHsd

cardiovascular system phenotype

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

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

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

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

immune system phenotype

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

The following phenotype relates to a compound genotype created using this strain

Genotype: Ccr5^tm1Kuz/Ccr5^tm1Kuz
B6.129P2-Ccr5

behavior/neurological phenotype

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

increased alcohol consumption
- in female but not male mice

increased fluid intake
- of an ethanol, saccharin, or quinine solution

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

vision/eye phenotype

corneal vascularization
- 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 phenotype

corneal vascularization
- 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

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

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

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

mammalian phenotype

behavior/neurological phenotype
- Normal - become catatonic and display staring behavior within 15 minutes
- Normal - myoclonic twitching, frequent rearing and falling
- Normal - response to kainic acid similar to controls
- Normal - seizures lasting up to 5 hours

mortality/aging
- Normal - 40% mortality after kainic acid treatment

nervous system phenotype
- Normal - selective CA3 hippocampal pycnosis after kainic acid treatment as in controls
- Normal - susceptibility of cerebral granule cell neurons to kainic acid is similar to controls

References

Kuziel WA; Dawson TC; Quinones M; Garavito E; Chenaux G; Ahuja SS; Reddick RL; Maeda N. 2003. CCR5 deficiency is not protective in the early stages of atherogenesis in apoE knockout mice. Atherosclerosis 167(1):25-32PubMed: 12618265 MGI: J:84243

Additional References

Kobayashi K; Umeda K; Ihara F; Tanaka S; Yamagishi J; Suzuki Y; Nishikawa Y. 2019. Transcriptome analysis of the effect of C-C chemokine receptor 5 deficiency on cell response to Toxoplasma gondii in brain cells. BMC Genomics 20(1):705PubMed: 31506064 MGI: J:290490
Maung R; Hoefer MM; Sanchez AB; Sejbuk NE; Medders KE; Desai MK; Catalan IC; Dowling CC; de Rozieres CM; Garden GA; Russo R; Roberts AJ; Williams R; Kaul M. 2014. CCR5 knockout prevents neuronal injury and behavioral impairment induced in a transgenic mouse model by a CXCR4-using HIV-1 glycoprotein 120. J Immunol 193(4):1895-910PubMed: 25031461 MGI: J:268960

Additional - Ccr5^tm1Kuz related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Ccr5
- Standard PCR:Ccr5 MCA
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

When maintaining a live colony, these mice are bred as homozygotes.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Citation
When using the CCR5 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #005427 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX11 (Maximum)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Ccr5<tm1Kuz>

Related Products and Services

Frozen Mouse Embryo	B6.129P2-Ccr5<tm1Kuz>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6.129P2-Ccr5<tm1Kuz>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6.129P2-Ccr5<tm1Kuz>/J Frozen Embryos	$3373.50
Frozen Mouse Embryo	B6.129P2-Ccr5<tm1Kuz>/J Frozen Embryos	$3373.50

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.

Animal Care and Use for SERVICES

Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.

Also Known As:CCR5 KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Ccr5tm1Kuz

Allele Symbol: Ccr5tm1Kuz

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Ccr5tm1Kuz related

Mammalian Phenotype Terms by Genotype

Genotype: Ccr5tm1Kuz/Ccr5tm1Kuzinvolves: 129P2/OlaHsd * C57BL/6

behavior/neurological phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

cardiovascular system phenotype

liver/biliary system phenotype

nervous system phenotype

cellular phenotype

digestive/alimentary phenotype

Genotype: Ccr5tm1Kuz/Ccr5tm1Kuzinvolves: 129P2/OlaHsd

cardiovascular system phenotype

homeostasis/metabolism phenotype

immune system phenotype

Genotype: Ccr5tm1Kuz/Ccr5tm1KuzB6.129P2-Ccr5

behavior/neurological phenotype

respiratory system phenotype

vision/eye phenotype

cardiovascular system phenotype

immune system phenotype

mammalian phenotype

References

Additional References

Additional - Ccr5tm1Kuz related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Ccr5^tm1Kuz

Allele Symbol: Ccr5^tm1Kuz

Genotype: Ccr5^tm1Kuz related

Genotype: Ccr5^tm1Kuz/Ccr5^tm1Kuz
involves: 129P2/OlaHsd * C57BL/6

Genotype: Ccr5^tm1Kuz/Ccr5^tm1Kuz
involves: 129P2/OlaHsd

Genotype: Ccr5^tm1Kuz/Ccr5^tm1Kuz
B6.129P2-Ccr5

Additional - Ccr5^tm1Kuz related