Overview

Also Known As: Ccl2 KO

Mice that are homozygous for the targeted mutation show similar numbers of peritoneal macrophages, Kupffer cell and alveolar macrophages to those observed in wildtype mice. Thioglycollate induced peritonitis results in impaired recruitment of monocytes and macrophages to peritoneal cavity. Cellular recruitment to delayed-type hypersensitivity challenges and secondary granulomata is reduced. This mutant mouse strain represents a model that may be useful in studies related to leukocyte trafficking.

Donating Investigator

Barrett J. Rollins, Dana-Farber Cancer Inst, Harvard Med Sch

Genetic overview

Genetic Background	Generation
	Contact Technical Support (2018-07-27 00:00:00)

Ccl2^tm1Rol

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Ccl2	chemokine (C-C motif) ligand 2

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Research Applications

Cancer Research
Immunology, Inflammation and Autoimmunity Research
Internal/Organ Research

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Base Price

Starting at:

$185.03 Domestic price for female 3-week

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Details

Detailed Description

Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product is detected in lipopolysaccharide (LPS) -stimulated peritoneal macrophages isolated from homozygous mice. The numbers of peritoneal macrophages, Kupffer cell and alveolar macrophages were similar to levels found in wildtype mice. Thioglycollate induced peritonitis results in impaired recruitment of monocytes and macrophages to peritoneal cavity. Cellular recruitment to delayed-type hypersensitivity challenges and secondary granulomata is reduced. This mutant mouse strain represents a model that may be useful in studies related to leukocyte trafficking.

Development

A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 2 and insert an inframe stop codon into exon 1. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to C57BL/6 for ten generations.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Lu B; Rutledge BJ; Gu L; Fiorillo J; Lukacs NW; Kunkel SL; North R; Gerard C; Rollins BJ. 1998. Abnormalities in monocyte recruitment and cytokine expression in monocyte chemoattractant protein 1-deficient mice. J Exp Med 187(4):601-8PubMed: 9463410 MGI: J:45920

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Genetics

Ccl2^tm1Rol

Allele Symbol: Ccl2^tm1Rol

Allele Name	targeted mutation 1, Barrett J Rollins
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Ccl2^tm1Rol; targeted mutation 1, Barrett J Rollins
Gene Symbol and Name	Ccl2, chemokine (C-C motif) ligand 2
Gene Synonym(s)	SMC-CF; NCC-1; expressed sequence AI323594; small inducible gene JE; NCC1; HC11; monocyte chemoattractant protein-1; monocyte chemotactic protein; Sigje; Scya2; SCYA13; SCYL1; Sigje; CKb10; AI323594; MCAF; MCP-1; MCP-4; MCP1; small inducible cytokine A2; HSMCR30; GDCF-2; SCYA2; Scya2
Strain of Origin	129S4/SvJae
Chromosome	11
Molecular Note	A small deletion and an in frame stop codon were created in exon 1. A PGK-neomycin resistance cassette was also inserted into exon 2. Secreted protein was not detected in stimulated peritoneal macrophages from homozygous mutant mice.
Mutations Made By	Barrett Rollins, Dana-Farber Cancer Inst, Harvard Med Sch

Disease/Phenotype

Disease Terms

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

age related macular degeneration

Research Areas By Genotype

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

Genotype: Ccl2^tm1Rol related

Cancer Research
- Growth Factors/Receptors/Cytokines
Immunology, Inflammation and Autoimmunity Research
- Inflammation
Internal/Organ Research
- Wound Healing
  - delayed/impaired

Mammalian Phenotype Terms by Genotype

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

Genotype: Ccl2^tm1Rol/Ccl2^tm1Rol
involves: 129S4/SvJae * 129X1/SvJ * C57BL/6

cellular phenotype

impaired macrophage chemotaxis
- impaired macrophage recruitment following intraperitoneal thioglycollate injection

hematopoietic system phenotype

abnormal monocyte morphology
- mutants are unable to recruit monocytes 72 hours after intraperitoneal thioglycollate administration despite normal numbers of circulating leukocytes and macrophages

impaired macrophage chemotaxis
- impaired macrophage recruitment following intraperitoneal thioglycollate injection

immune system phenotype

abnormal monocyte morphology
- mutants are unable to recruit monocytes 72 hours after intraperitoneal thioglycollate administration despite normal numbers of circulating leukocytes and macrophages

decreased interferon-gamma secretion
- IFN-gamma secretion is 59% lower in mutant splenocytes

decreased interleukin-4 secretion
- IL-4 production is reduced in splenocytes

decreased interleukin-5 secretion
- IL-5 production is reduced in splenocytes

decreased susceptibility to type IV hypersensitivity reaction
- accumulation of F4/80+ monocytes in delayed-type hypersensitivity lesions is impaired, although the swelling response is normal
- development of secondary pulmonary granulomata in response to Schistosoma mansoni eggs in blunted

impaired macrophage chemotaxis
- impaired macrophage recruitment following intraperitoneal thioglycollate injection

Genotype: Ccl2^tm1Rol/Ccl2^tm1Rol
involves: 129S4/SvJae * C57BL/6

cardiovascular system phenotype

abnormal heart left ventricle morphology
- following myocardial infarction, mice exhibit lower left ventricle end diastolic diameter compared with similarly treated wild-type mice

abnormal physiological neovascularization
- ischemic capillary density relative to nonischemic density 30% lower than in controls
- poor recovery of blood flow after ischemia

altered response to myocardial infarction
- following myocardial infarction, mice exhibit decreased myofibroblast infiltration 3 days after reperfusion compared with similarly treated wild-type mice
- following myocardial infarction, mice exhibit impaired macrophage recruitment with delayed peak macrophage numbers compared with similarly treated wild-type mice
- following myocardial infarction, mice exhibit lower left ventricle end diastolic diameter compared with similarly treated wild-type mice
- following myocardial infarction, mice exhibit persistence of dead cardiomyocytes and delayed replacement with granulation compared with similarly treated wild-type mice
- Normal - however, mice exhibit normal macrophage density, infarct size, and angiogenesis following myocardial infarction

digestive/alimentary phenotype

decreased susceptibility to induced colitis
- DNBS-treated mice exhibit reduced mucosal damage; less thickening of the colonic wall; less goblet cell depletion; fewer adhesions; reduced macrophage and CD3+ T cell infiltration; reduced IL1beta, IL12p40, and ConA-stimulated production; reduced numbers of 5-HT-expressing enterochromaffin cells, and no increase in mortality compared with similarly treated wild-type mice
- of 5-HT-expressing enterochromaffin cells, and no increase in mortality compared with similarly treated wild-type mice

hematopoietic system phenotype

abnormal macrophage chemotaxis
- in colonic tissue following DNBS treatment

abnormal T cell physiology
- following DNBS treatment, infiltration of CD3+ T cells in colonic tissue is decreased compared to in wild-type mice

impaired macrophage chemotaxis
- following myocardial infarction, mice exhibit impaired macrophage recruitment with delayed peak macrophage numbers compared with similarly treated wild-type mice
- Normal - however, macrophage density is normal 3 to 7 days following myocardial infarction

homeostasis/metabolism phenotype

altered response to myocardial infarction
- following myocardial infarction, mice exhibit decreased myofibroblast infiltration 3 days after reperfusion compared with similarly treated wild-type mice
- following myocardial infarction, mice exhibit impaired macrophage recruitment with delayed peak macrophage numbers compared with similarly treated wild-type mice
- following myocardial infarction, mice exhibit lower left ventricle end diastolic diameter compared with similarly treated wild-type mice
- following myocardial infarction, mice exhibit persistence of dead cardiomyocytes and delayed replacement with granulation compared with similarly treated wild-type mice
- Normal - however, mice exhibit normal macrophage density, infarct size, and angiogenesis following myocardial infarction

decreased incidence of tumors by chemical induction
- DMBA and TPA-treated mice exhibit 50% fewer skin tumors than similarly treated wild-type mice

decreased sensitivity to xenobiotic induced morbidity/mortality
- DNBS-treated mice do not exhibit an increase in mortality compared with similarly treated wild-type mice

immune system phenotype

abnormal macrophage chemotaxis
- in colonic tissue following DNBS treatment

abnormal T cell physiology
- following DNBS treatment, infiltration of CD3+ T cells in colonic tissue is decreased compared to in wild-type mice

decreased interferon-gamma secretion
- in ConA-treated splenic cells of DNBS-treated mice

decreased interleukin-1 beta secretion
- in colonic tissue following DNBS treatment

decreased interleukin-12b secretion
- in colonic tissue following DNBS treatment

decreased susceptibility to induced colitis
- DNBS-treated mice exhibit reduced mucosal damage; less thickening of the colonic wall; less goblet cell depletion; fewer adhesions; reduced macrophage and CD3+ T cell infiltration; reduced IL1beta, IL12p40, and ConA-stimulated production; reduced numbers of 5-HT-expressing enterochromaffin cells, and no increase in mortality compared with similarly treated wild-type mice
- of 5-HT-expressing enterochromaffin cells, and no increase in mortality compared with similarly treated wild-type mice

impaired macrophage chemotaxis
- following myocardial infarction, mice exhibit impaired macrophage recruitment with delayed peak macrophage numbers compared with similarly treated wild-type mice
- Normal - however, macrophage density is normal 3 to 7 days following myocardial infarction

mortality/aging

decreased sensitivity to xenobiotic induced morbidity/mortality
- DNBS-treated mice do not exhibit an increase in mortality compared with similarly treated wild-type mice

neoplasm

decreased incidence of tumors by chemical induction
- DMBA and TPA-treated mice exhibit 50% fewer skin tumors than similarly treated wild-type mice

cellular phenotype

abnormal macrophage chemotaxis
- in colonic tissue following DNBS treatment

impaired macrophage chemotaxis
- following myocardial infarction, mice exhibit impaired macrophage recruitment with delayed peak macrophage numbers compared with similarly treated wild-type mice
- Normal - however, macrophage density is normal 3 to 7 days following myocardial infarction

Genotype: Ccl2^tm1Rol/Ccl2^tm1Rol
involves: 129S4/SvJae

behavior/neurological phenotype

abnormal posture
- following infection with T. cruzi, mice exhibit prostration as they near death unlike similarly treated wild-type mice

homeostasis/metabolism phenotype

decreased physiological sensitivity to xenobiotic
- mice are protected from bleomycin-induced lung fibrosis with fewer recruited alveolar macrophages and lymphocytes in the lungs compared with similarly treated wild-type mice

increased circulating interferon-gamma level
- following infection with T. cruzi

increased circulating interleukin-10 level
- following infection with T. cruzi

increased circulating tumor necrosis factor level
- following infection with T. cruzi

immune system phenotype

abnormal macrophage physiology
- activated macrophage clear trypomastigotes less efficiently than wild-type cells

abnormal monocyte morphology
- 7/4^bri and 7/4^dim cells are decreased in blood by 50%
- intraperitoneal thioglycollate challenge leads to an increase in 7/4^bri cells

decreased inflammatory response
- following infection with T. cruzi, mice exhibit decreased focal infiltration of leukocytes (recruitment of activated CD8+ cells and monocytes) in the heart and liver compared with similarly treated wild-type mice

decreased lymphocyte cell number
- in the bronchoalveolar lavage of bleomycin-treated mice compared with similarly treated wild-type mice

decreased macrophage cell number
- in the bronchoalveolar lavage of bleomycin-treated mice compared with similarly treated wild-type mice

impaired macrophage chemotaxis
- to the lungs of bleomycin-treated mice compared with similarly treated wild-type mice

increased circulating interferon-gamma level
- following infection with T. cruzi

increased circulating interleukin-10 level
- following infection with T. cruzi

increased circulating tumor necrosis factor level
- following infection with T. cruzi

increased susceptibility to infection induced morbidity/mortality
- following infection with the parasite T. cruzi, mice exhibit earlier and increased lethality compared with similarly treated wild-type mice

increased susceptibility to parasitic infection
- d unlike in similarly treated wild-type mice
- mice infected with T. cruzi exhibit increased mortality; prostration, vasodilation and rough hair close to the time of death; increased plasma TNF, IFN-gamma, and IL10 levels; increased tissue parasitic burden with reduced focal leukocyte infiltration; and unlike in similarly treated wild-type mice

cardiovascular system phenotype

increased vasodilation
- following infection with T. cruzi as mice near death

mortality/aging

increased susceptibility to infection induced morbidity/mortality
- following infection with the parasite T. cruzi, mice exhibit earlier and increased lethality compared with similarly treated wild-type mice

muscle phenotype

increased vasodilation
- following infection with T. cruzi as mice near death

cellular phenotype

impaired macrophage chemotaxis
- to the lungs of bleomycin-treated mice compared with similarly treated wild-type mice

hematopoietic system phenotype

abnormal macrophage physiology
- activated macrophage clear trypomastigotes less efficiently than wild-type cells

abnormal monocyte morphology
- 7/4^bri and 7/4^dim cells are decreased in blood by 50%
- intraperitoneal thioglycollate challenge leads to an increase in 7/4^bri cells

decreased lymphocyte cell number
- in the bronchoalveolar lavage of bleomycin-treated mice compared with similarly treated wild-type mice

decreased macrophage cell number
- in the bronchoalveolar lavage of bleomycin-treated mice compared with similarly treated wild-type mice

impaired macrophage chemotaxis
- to the lungs of bleomycin-treated mice compared with similarly treated wild-type mice

Genotype: Ccl2^tm1Rol/Ccl2^tm1Rol
SJL.129S4-Ccl2

immune system phenotype

decreased susceptibility to experimental autoimmune encephalomyelitis
- homozygotes exhibit attenuated severity of PLP-induced EAE and reduced number of relapses compared to wild-type

Genotype: Ccl2^tm1Rol/Ccl2^tm1Rol
(129S4/SvJae x C57BL/6)F1

hematopoietic system phenotype

decreased macrophage cell number
- following induction of nephrotoxic serum nephritis, mice exhibit reduced macrophage accumulation in the interstitium and adjacent to damaged tubules compared with similarly treated wild-type mice
- Normal - however, the number macrophages in the glomeruli is normal following induction of nephrotoxic serum nephritis

homeostasis/metabolism phenotype

abnormal response to injury
- following induction of nephrotoxic serum nephritis, mice exhibit reduced tubule damage and macrophage accumulation compared with similarly treated wild-type mice
- Normal - however, mice exhibit normal IgG/C3 deposition, proteinuria, glomerular macrophage accumulation, and glomerular damage following induction of nephrotoxic serum nephritis

immune system phenotype

decreased macrophage cell number
- following induction of nephrotoxic serum nephritis, mice exhibit reduced macrophage accumulation in the interstitium and adjacent to damaged tubules compared with similarly treated wild-type mice
- Normal - however, the number macrophages in the glomeruli is normal following induction of nephrotoxic serum nephritis

Genotype: Ccl2^tm1Rol/Ccl2^tm1Rol
involves: 129S4/SvJae * C57BL/6 * SJL

cardiovascular system phenotype

decreased angiogenesis
- during wound healing

homeostasis/metabolism phenotype

delayed wound healing
- at day 3 following injury, re-epithelialization is delayed with decreased vascular density at the injury compared to in similarly treated wild-type mice
- complete wound healing takes twice as long as in wild-type mice
- Normal - however, macrophage accumulation at the site of injury is normal

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

Genotype: Ccl2^tm1Rol/Ccl2^tm1Rol
B6.129S4-Ccl2

behavior/neurological phenotype

abnormal conditioned taste aversion behavior
- Normal - however, saccharin consumption is normal
- mice exhibit a stronger response to ethanol in an ethanol-induced conditioned taste aversion test compared with similarly treated wild-type mice

alcohol aversion
- in female mice

alcohol preference
- female mice exhibit a greater ethanol preference compared with Ccl2^tm1Rol Ccr2^tm1Mae double homozygotes and Ccr2^tm1Mae homozygotes
- male mice exhibit a greater ethanol preference compared with wild-type (in post hoc analysis) mice, Ccr2^tm1Mae homozygotes, and Ccl2^tm1Rol Ccr2^tm1Mae double homozygotes

decreased alcohol consumption
- in female mice compared with wild-type mice and Ccr2^tm1Mae homozygotes

impaired righting response
- mice exhibit longer duration of ethanol-induced loss of righting response compared with similarly treated wild-type mice

increased alcohol consumption
- female mice consume more ethanol than Ccl2^tm1Rol Ccr2^tm1Mae double homozygotes
- male mice consume more ethanol than wild-type (in post hoc analysis) mice and Ccl2^tm1Rol Ccr2^tm1Mae double homozygotes

increased fluid intake
- mice exhibit increased drinking of a quinine solution compared with wild-type mice
- mice exhibit increased drinking of an ethanol solution compared with Ccl2^tm1Rol Ccr2^tm1Mae double homozygotes and Ccr2^tm1Mae homozygotes

cardiovascular system phenotype

abnormal blood circulation
- following femoral artery excision, mice exhibit a delay in the restoration of perfusion compared with similarly treated wild-type mice

abnormal choriocapillaris morphology
- at 16 months, mice exhibit dilation and attenuation of the choriocapillaris unlike wild-type mice

choroidal neovascularization
- after 18 months, 4 of 15 mice exhibit choroidal neovascularization with angiographic leakage unlike in wild-type mice
- at 15 to 19 months, mice exhibit intrachoroidal neovascularization with angiographic leakage unlike wild-type mice
- between 18 and 27 months, neovasculatization breaches the Bruch membrane and causes retinal pigmented epithelium and photoreceptor disruptions unlike in wild-type mice

cellular phenotype

abnormal macrophage chemotaxis
- the timing of macrophage recruitment during tooth eruption is different than in wild-type mice with peak numbers occurring earlier than in wild-type mice
- Normal - the total number of macrophages recruited is normal

impaired macrophage chemotaxis
- initially following femoral artery excision
- mutants show impaired macrophage recruitment to the CNS after MOG35-55 induced EAE
- only half the number of macrophages are recruited to the peritoneum in an induced peritonitis model as occurs in wild-type controls

skeletal muscle necrosis
- following femoral artery excision

craniofacial phenotype

premature tooth eruption
- from P16 to P18, mice exhibit a 31-fold increase in erupted cusps compared with wild-type mice
- tooth eruption begins at P14 instead of P16 as in wild-type mice

growth/size/body region phenotype

premature tooth eruption
- from P16 to P18, mice exhibit a 31-fold increase in erupted cusps compared with wild-type mice
- tooth eruption begins at P14 instead of P16 as in wild-type mice

hematopoietic system phenotype

abnormal macrophage chemotaxis
- the timing of macrophage recruitment during tooth eruption is different than in wild-type mice with peak numbers occurring earlier than in wild-type mice
- Normal - the total number of macrophages recruited is normal

abnormal neutrophil physiology
- the number of neutrophils recruited to the peritoneum in an induced peritonitis model is almost double that controls

decreased leukocyte cell number
- numbers of leukocytes isolated from CNS tissue during EAE attacks are about 1/3 of those from wild type mice with comparable EAE severity

decreased macrophage cell number
- age-dependent accumulation of macrophages in the choroids is less than in wild-type mice

impaired macrophage chemotaxis
- initially following femoral artery excision
- mutants show impaired macrophage recruitment to the CNS after MOG35-55 induced EAE
- only half the number of macrophages are recruited to the peritoneum in an induced peritonitis model as occurs in wild-type controls

increased CD4-positive, alpha beta T cell number
- in an EAE model, mutants show an increase in proportion of CD4+ cells and reduction in CD11b+CD4- in the CNS leukocyte infiltrates compared to wild-type, although total numbers of T cells are not different

increased IgG level
- at 16 months, IgG is present in the retinal pigmented epithelium or choroids unlike in wild-type mice
- IgG light chain deposition in the retinal pigmented epithelium accumulates with age unlike in wild-type mice

increased IgG1 level
- significantly higher levels of anti-MOG35-55 IgG1 antibodies are seen in mutants compared to wild-type

increased neutrophil cell number
- 1 and 3 days after femoral artery excision, mice exhibit an earlier increase in neutrophil accumulation (measured by MPO activity) than in similarly treated wild-type mice

increased osteoclast cell number
- at P5 during tooth eruption
- peak osteoclast accumulation occurs at P5 instead of at P9 as in wild-type mice

homeostasis/metabolism phenotype

abnormal chemokine level
- 1 day after femoral artery excision, muscles accumulate more chemoattractants (KC and MIP-2) than in similarly treated wild-type mice
- in thioglycollate- or zymosan- induced peritonitis models, no Ccl2 is detected while reduce levels of Ccl7 are present in peritoneal fluid

abnormal response to injury
- compared with similarly treated wild-type mice
- following femoral artery excision, mice exhibit a delay in the restoration of perfusion, extended period of increased ischemic muscle weight at day 1 and 7, earlier increase in neutrophil accumulation (measured by MPO activity) at day 1 and 3, increased chemoattractants (KC and MIP-2) levels at day 1, decreased accumulation of inflammatory infiltrate at day 3, delayed macrophage recruitment, large regions of necrotic muscle, increased adipocyte accumulation in the muscle, and impaired muscle regeneration compared with similarly treated wild-type mice
- hemoattractants (KC and MIP-2) levels at day 1, decreased accumulation of inflammatory infiltrate at day 3, delayed macrophage recruitment, large regions of necrotic muscle, increased adipocyte accumulation in the muscle, and impaired muscle regeneration

decreased physiological sensitivity to xenobiotic
- bleomycin-treated mice fail to exhibit skin fibrosis with normal collagen fibrils and few infiltrating macrophages and neutrophils unlike similarly treated wild-type mice

immune system phenotype

abnormal chemokine level
- 1 day after femoral artery excision, muscles accumulate more chemoattractants (KC and MIP-2) than in similarly treated wild-type mice
- in thioglycollate- or zymosan- induced peritonitis models, no Ccl2 is detected while reduce levels of Ccl7 are present in peritoneal fluid

abnormal chemokine secretion
- secretion of Ccl7 (MCP-3) and Ccl12 (MCP-5) is also dramatically reduced by these activated macrophages
- there is no Ccl2 (MCP-1) secretion by peritoneal macrophages activated in vitro compared to controls

abnormal cytokine secretion
- MOG35-55-specific Th1 cytokine responses are diminished in mutants

abnormal macrophage chemotaxis
- the timing of macrophage recruitment during tooth eruption is different than in wild-type mice with peak numbers occurring earlier than in wild-type mice
- Normal - the total number of macrophages recruited is normal

abnormal neutrophil physiology
- the number of neutrophils recruited to the peritoneum in an induced peritonitis model is almost double that controls

decreased interferon-gamma secretion
- mutants exhibit reduced production of IFN-gamma in response to MOG35-55 induced EAE

decreased leukocyte cell number
- numbers of leukocytes isolated from CNS tissue during EAE attacks are about 1/3 of those from wild type mice with comparable EAE severity

decreased macrophage cell number
- age-dependent accumulation of macrophages in the choroids is less than in wild-type mice

decreased susceptibility to experimental autoimmune encephalomyelitis
- adoptive transfer of primed T cells from wild-type mice to naive homozygous mutant recipients does not mediate clinical EAE, however wild-type mice receiving mutant T cells do develop clinical EAE
- d faster and complete recovery
- homozygotes are resistant to active experimental autoimmune encephalomyelitis (EAE) induction with MOG35-55, with delayed onset of disease, reduced inflammatory reaction including impaired recruitment of macrophages to the central nervous system (CNS), and faster and complete recovery

impaired macrophage chemotaxis
- initially following femoral artery excision
- mutants show impaired macrophage recruitment to the CNS after MOG35-55 induced EAE
- only half the number of macrophages are recruited to the peritoneum in an induced peritonitis model as occurs in wild-type controls

increased CD4-positive, alpha beta T cell number
- in an EAE model, mutants show an increase in proportion of CD4+ cells and reduction in CD11b+CD4- in the CNS leukocyte infiltrates compared to wild-type, although total numbers of T cells are not different

increased IgG level
- at 16 months, IgG is present in the retinal pigmented epithelium or choroids unlike in wild-type mice
- IgG light chain deposition in the retinal pigmented epithelium accumulates with age unlike in wild-type mice

increased IgG1 level
- significantly higher levels of anti-MOG35-55 IgG1 antibodies are seen in mutants compared to wild-type

increased interleukin-10 secretion
- mutants exhibit enhanced secretion of IL-10 in response to MOG35-55 induced EAE

increased neutrophil cell number
- 1 and 3 days after femoral artery excision, mice exhibit an earlier increase in neutrophil accumulation (measured by MPO activity) than in similarly treated wild-type mice

increased osteoclast cell number
- at P5 during tooth eruption
- peak osteoclast accumulation occurs at P5 instead of at P9 as in wild-type mice

muscle phenotype

abnormal skeletal muscle morphology
- following femoral artery excision, muscles accumulate more adipocytes than in similarly treated wild-type mice

abnormal skeletal muscle regeneration
- muscle regeneration, as measured by LDH and fiber size, is impaired following femoral artery excision

increased muscle weight
- after 1 and 7 days, mice subjected to femoral artery excision exhibit an extended period of increased ischemic muscle weight compared with similarly treated wild-type mice

skeletal muscle necrosis
- following femoral artery excision

nervous system phenotype

retinal photoreceptor degeneration
- at 16 months

pigmentation phenotype

abnormal retinal pigment epithelium morphology
- after 9 months of age, lipofuscin granules are observed in the swollen and vacuolated retinal pigmented epithelial cells unlike in wild-type mice
- at 16 months, mice exhibit attenuation of the retinal pigmented epithelium unlike in wild-type mice

lipofuscinosis
- after 9 months of age, lipofuscin granules are observed in the swollen and vacuolated retinal pigmented epithelial cells unlike in wild-type mice

skeleton phenotype

increased osteoclast cell number
- at P5 during tooth eruption
- peak osteoclast accumulation occurs at P5 instead of at P9 as in wild-type mice

premature tooth eruption
- from P16 to P18, mice exhibit a 31-fold increase in erupted cusps compared with wild-type mice
- tooth eruption begins at P14 instead of P16 as in wild-type mice

vision/eye phenotype

abnormal Bruch membrane morphology
- at 20 months, the outer Bruch membrane is breached by choriocapillary processes unlike in wild-type mice
- the Bruch membrane is thickened compared to in wild-type mice after 9 months of age

abnormal choriocapillaris morphology
- at 16 months, mice exhibit dilation and attenuation of the choriocapillaris unlike wild-type mice

abnormal optic choroid morphology
- age-dependent accumulation of macrophages in the choroids is less than in wild-type mice

abnormal retinal pigment epithelium morphology
- after 9 months of age, lipofuscin granules are observed in the swollen and vacuolated retinal pigmented epithelial cells unlike in wild-type mice
- at 16 months, mice exhibit attenuation of the retinal pigmented epithelium unlike in wild-type mice

choroidal neovascularization
- after 18 months, 4 of 15 mice exhibit choroidal neovascularization with angiographic leakage unlike in wild-type mice
- at 15 to 19 months, mice exhibit intrachoroidal neovascularization with angiographic leakage unlike wild-type mice
- between 18 and 27 months, neovasculatization breaches the Bruch membrane and causes retinal pigmented epithelium and photoreceptor disruptions unlike in wild-type mice

retinal degeneration
- at 16 months, mice exhibit progressive outer retinal degeneration and confluent areas of visible atrophy unlike in wild-type mice
- at 18 months, mice exhibit geographic atrophy unlike in wild-type mice

retinal deposits
- after 9 months of age, mice exhibit subretinal deposits similar to drusen that increase with age unlike in wild-type mice

retinal outer nuclear layer degeneration
- at 16 months

retinal photoreceptor degeneration
- at 16 months

Genotype: Ccl2^tm1Rol/Ccl2^tm1Rol
B6.129S4-Ccl2/J

adipose tissue phenotype

abnormal epididymal fat pad morphology
- when fed a high fat diet, macrophage infiltration of the epididymal fat pad is reduced compared to in similarly treated wild-type mice

abnormal gonadal fat pad morphology
- Normal - however, macrophage numbers in subcutaneous fat when fed a standard diet is normal
- mice fed a high fat diet exhibit a mild increase in macrophage infiltration of adipose tissue compared with similarly treated wild-type mice

decreased fat cell size
- when mice are fed a high fat diet compared with similarly treated wild-type mice

increased percent body fat/body weight
- 15% in mice fed a high fat diet compared with similarly treated wild-type mice

increased total fat pad weight
- when fed a high fat diet

hematopoietic system phenotype

abnormal microglial cell physiology
- mice treated with kainate acid exhibit decreased microglial accumulation compared with similarly treated wild-type mice

homeostasis/metabolism phenotype

abnormal gluconeogenesis
- during hyperinsulinemic-euglycemic clamp analysis, mice fed a high fat diet exhibit a 3-fold increase in basal and clamp hepatic glucose production compared with similarly treated wild-type mice

abnormal glucose homeostasis

decreased adiponectin level
- regardless of diet

decreased circulating free fatty acid level
- when mice are fed a high fat diet compared with similarly treated wild-type mice

decreased circulating insulin level
- when mice are fed a high fat diet compared with similarly treated wild-type mice

decreased susceptibility to neuronal excitotoxicity
- mice treated with kainate acid exhibit decreased microglial accumulation and reduced neurodegeneration in the CA1 and CA3 pyramidal neurons compared with similarly treated wild-type mice

impaired glucose tolerance
- at 14 and 27 weeks regardless of diet

improved glucose tolerance
- when mice are fed a high fat diet compared with similarly treated wild-type mice

increased adiponectin level
- when mice are fed a high fat diet compared with similarly treated wild-type mice

increased circulating glucose level
- mild in fasting mice regardless of diet

increased circulating insulin level
- when fed a high fat diet

increased circulating leptin level
- when fed a high fat diet

increased insulin sensitivity
- when mice are fed a high fat diet compared with similarly treated wild-type mice

increased susceptibility to diet-induced obesity
- at 18 to 34 weeks, mice fed a high fat diet exhibit a 13% increase in body weight compared with similarly treated wild-type mice
- when fed a high fat diet, mice exhibit a mildly enhanced weight gain compared with similarly treated wild-type mice

immune system phenotype

abnormal microglial cell physiology
- mice treated with kainate acid exhibit decreased microglial accumulation compared with similarly treated wild-type mice

liver/biliary system phenotype

decreased susceptibility to hepatic steatosis
- when mice are fed a high fat diet compared with similarly treated wild-type mice

nervous system phenotype

abnormal microglial cell physiology
- mice treated with kainate acid exhibit decreased microglial accumulation compared with similarly treated wild-type mice

decreased susceptibility to neuronal excitotoxicity
- mice treated with kainate acid exhibit decreased microglial accumulation and reduced neurodegeneration in the CA1 and CA3 pyramidal neurons compared with similarly treated wild-type mice

cellular phenotype

decreased susceptibility to neuronal excitotoxicity
- mice treated with kainate acid exhibit decreased microglial accumulation and reduced neurodegeneration in the CA1 and CA3 pyramidal neurons compared with similarly treated wild-type mice

growth/size/body region phenotype

decreased body weight
- slightly when mice are fed a standard diet

increased susceptibility to diet-induced obesity
- at 18 to 34 weeks, mice fed a high fat diet exhibit a 13% increase in body weight compared with similarly treated wild-type mice
- when fed a high fat diet, mice exhibit a mildly enhanced weight gain compared with similarly treated wild-type mice

References

Lu B; Rutledge BJ; Gu L; Fiorillo J; Lukacs NW; Kunkel SL; North R; Gerard C; Rollins BJ. 1998. Abnormalities in monocyte recruitment and cytokine expression in monocyte chemoattractant protein 1-deficient mice. J Exp Med 187(4):601-8PubMed: 9463410 MGI: J:45920

Additional References

Cambre I; Gaublomme D; Burssens A; Jacques P; Schryvers N; De Muynck A; Meuris L; Lambrecht S; Carter S; de Bleser P; Saeys Y; Van Hoorebeke L; Kollias G; Mack M; Simoens P; Lories R; Callewaert N; Schett G; Elewaut D. 2018. Mechanical strain determines the site-specific localization of inflammation and tissue damage in arthritis. Nat Commun 9(1):4613PubMed: 30397205 MGI: J:268554
Liao C; Prabhu KS; Paulson RF. 2018. Monocyte-derived macrophages expand the murine stress erythropoietic niche during the recovery from anemia. Blood 132(24):2580-2593PubMed: 30322871 MGI: J:268964
Huang D; Wang J; Kivisakk P; Rollins BJ; Ransohoff RM. 2001. Absence of monocyte chemoattractant protein 1 in mice leads to decreased local macrophage recruitment and antigen-specific t helper cell type 1 immune response in experimental autoimmune encephalomyelitis. J Exp Med 193(6):713-26PubMed: 11257138 MGI: J:68145
Low QE; Drugea IA; Duffner LA; Quinn DG; Cook DN; Rollins BJ; Kovacs EJ; DiPietro LA. 2001. Wound healing in MIP-1alpha(-/-) and MCP-1(-/-) mice. Am J Pathol 159(2):457-63PubMed: 11485904 MGI: J:70862
Kawakami K; Kinjo Y; Uezu K; Yara S; Miyagi K; Koguchi Y; Nakayama T; Taniguchi M; Saito A. 2001. Monocyte chemoattractant protein-1-dependent increase of Valpha14 NKT cells in lungs and their roles in Th1 response and host defense in cryptococcal infection. J Immunol 167(11):6525-32PubMed: 11714821 MGI: J:72823
Gu L; Okada Y; Clinton SK; Gerard C; Sukhova GK; Libby P; Rollins BJ. 1998. Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low density lipoprotein receptor-deficient mice. Mol Cell 2(2):275-81PubMed: 9734366 MGI: J:75837
Muessel MJ; Klein RM; Wilson AM; Berman NE. 2002. Ablation of the chemokine monocyte chemoattractant protein-1 delays retrograde neuronal degeneration, attenuates microglial activation, and alters expression of cell death molecules. Brain Res Mol Brain Res 103(1-2):12-27PubMed: 12106688 MGI: J:78320
Gonnella PA; Kodali D; Weiner HL. 2003. Induction of low dose oral tolerance in monocyte chemoattractant protein-1- and CCR2-deficient mice. J Immunol 170(5):2316-22PubMed: 12594253 MGI: J:82016

Additional - Ccl2^tm1Rol related

Technical Support

Contact Technical Support

Genotyping Protocols
- End Point Analysis: Crb1^rd8End Point
- Melt Curve Analysis: Ccl2^tm1Rol
- Standard PCR: Ccl2^tm1Rol
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

This strain is a good breeder.

When maintaining a live colony, homozygous mice may be bred together. The expected coat color is Black.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Citation
When using the Ccl2 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004434 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX8 (Standard)

Pricing & Availability

Available Now

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous for Ccl2<tm1Rol>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

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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.

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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.

Terms Of Use

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

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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

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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: Ccl2 KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Ccl2tm1Rol

Allele Symbol: Ccl2tm1Rol

Disease Terms

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

Research Areas By Genotype

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

Genotype: Ccl2tm1Rol related

Mammalian Phenotype Terms by Genotype

Genotype: Ccl2tm1Rol/Ccl2tm1Rolinvolves: 129S4/SvJae * 129X1/SvJ * C57BL/6

cellular phenotype

hematopoietic system phenotype

immune system phenotype

Genotype: Ccl2tm1Rol/Ccl2tm1Rolinvolves: 129S4/SvJae * C57BL/6

cardiovascular system phenotype

digestive/alimentary phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

mortality/aging

neoplasm

cellular phenotype

Genotype: Ccl2tm1Rol/Ccl2tm1Rolinvolves: 129S4/SvJae

behavior/neurological phenotype

homeostasis/metabolism phenotype

immune system phenotype

cardiovascular system phenotype

mortality/aging

muscle phenotype

cellular phenotype

hematopoietic system phenotype

Genotype: Ccl2tm1Rol/Ccl2tm1RolSJL.129S4-Ccl2

immune system phenotype

Genotype: Ccl2tm1Rol/Ccl2tm1Rol(129S4/SvJae x C57BL/6)F1

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

Genotype: Ccl2tm1Rol/Ccl2tm1Rolinvolves: 129S4/SvJae * C57BL/6 * SJL

cardiovascular system phenotype

homeostasis/metabolism phenotype

Genotype: Ccl2tm1Rol/Ccl2tm1RolB6.129S4-Ccl2

behavior/neurological phenotype

cardiovascular system phenotype

cellular phenotype

craniofacial phenotype

growth/size/body region phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

muscle phenotype

nervous system phenotype

pigmentation phenotype

skeleton phenotype

vision/eye phenotype

Genotype: Ccl2tm1Rol/Ccl2tm1RolB6.129S4-Ccl2/J

adipose tissue phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

liver/biliary system phenotype

nervous system phenotype

cellular phenotype

growth/size/body region phenotype

References

Additional References

Additional - Ccl2tm1Rol related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Ccl2^tm1Rol

Allele Symbol: Ccl2^tm1Rol

Genotype: Ccl2^tm1Rol related

Genotype: Ccl2^tm1Rol/Ccl2^tm1Rol
involves: 129S4/SvJae * 129X1/SvJ * C57BL/6

Genotype: Ccl2^tm1Rol/Ccl2^tm1Rol
involves: 129S4/SvJae * C57BL/6

Genotype: Ccl2^tm1Rol/Ccl2^tm1Rol
involves: 129S4/SvJae

Genotype: Ccl2^tm1Rol/Ccl2^tm1Rol
SJL.129S4-Ccl2

Genotype: Ccl2^tm1Rol/Ccl2^tm1Rol
(129S4/SvJae x C57BL/6)F1

Genotype: Ccl2^tm1Rol/Ccl2^tm1Rol
involves: 129S4/SvJae * C57BL/6 * SJL

Genotype: Ccl2^tm1Rol/Ccl2^tm1Rol
B6.129S4-Ccl2

Genotype: Ccl2^tm1Rol/Ccl2^tm1Rol
B6.129S4-Ccl2/J

Additional - Ccl2^tm1Rol related