Strain Detail Sheet

Strain Name    :

B6.129P2-Ccr2tm1Mae/Mmnc

Stock Number :

000012-UNC

Gene Information

Gene Details [Including genotyping protocols]

(provided by MGI)
Allele Symbol: Ccr2tm1Mae
Name: targeted mutation 1, Nobuyo Maeda
Alteration at locus: Knockout
Gene Symbol: Ccr2
Name: chemokine (C-C motif) receptor 2
Chromosome: 9
Alteration at locus: Knockout

Genetic Alterations:
A pgk-neo cassette was inserted into the CCR2 coding region, disrupting the transcription.

Genotype Determination:

ES Cell Line: E14TG2a derived from B6;129P2

Strain Description [Including phenotype, strain background, strain development and suggested control mice]

Phenotype

Phenotypes include: reduced monocyte extravasation, delayed atherosclerosis development, and delayed neutorphil clearance after inflammation.


Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype
Ccr2tm1Mae/Ccr2tm1Mae
        B6.129P2-Ccr2<tm1Mae>
  • vision/eye phenotype
    • abnormal choroid morphology (MGI Ref ID J:147328)
      • age-dependent accumulation of macrophages in the choroids is less than in wild-type mice
      • abnormal Bruch membrane morphology (MGI Ref ID J:147328)
        • the Bruch membrane is thickened compared to in wild-type mice after 9 months of age
        • at 20 months, the outer Bruch membrane is breached by choriocapillary processes unlike in wild-type mice
      • abnormal choriocapillaris morphology (MGI Ref ID J:147328)
        • at 16 months, mice exhibit dilation and attenuation of the choriocapillaris unlike wild-type mice
      • choroidal neovascularization (MGI Ref ID J:147328)
        • at 15 to 19 months, mice exhibit intrachoroidal neovascularization with angiographic leakage unlike wild-type mice
        • after 18 months, 3 of 13 mice exhibit choroidal neovascularization with angiographic leakage unlike in 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
    • abnormal retinal pigment epithelium morphology (MGI Ref ID J:147328)
      • 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
    • retinal degeneration (MGI Ref ID J:147328)
      • 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 (MGI Ref ID J:147328)
      • 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 (MGI Ref ID J:147328)
      • at 16 months
    • retinal photoreceptor degeneration (MGI Ref ID J:147328)
      • at 16 months
  • behavior/neurological phenotype
    • abnormal conditioned taste aversion behavior (MGI Ref ID J:102583)
      • mice develop a stronger ethanol-induced conditioned taste aversion compared with similarly treated wild-type mice
    • alcohol aversion (MGI Ref ID J:102583)
      • mice exhibit decreased preference for ethanol water compared with wild-type mice
      • female mice exhibit a lesser ethanol preference compared with Ccl2tm1Rol Ccr2tm1Mae double homozygotes
    • decreased alcohol consumption (MGI Ref ID J:102583)
    • increased drinking behavior (MGI Ref ID J:102583)
      • mice exhibit increased drinking of an ethanol solution compared with wild-type mice and Ccl2tm1Rol Ccr2tm1Mae double homozygotes
      • mice exhibit increased drinking of a quinine solution compared with wild-type mice
      • increased alcohol consumption (MGI Ref ID J:102583)
        • in male mice compared with Ccl2tm1Rol Ccr2tm1Mae double homozygotes
  • immune system phenotype
    • decreased macrophage cell number (MGI Ref ID J:147328)
      • age-dependent accumulation of macrophages in the choroids is less than in wild-type mice
    • increased IgG level (MGI Ref ID J:147328)
      • 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
  • cardiovascular system phenotype
    • abnormal choriocapillaris morphology (MGI Ref ID J:147328)
      • at 16 months, mice exhibit dilation and attenuation of the choriocapillaris unlike wild-type mice
    • choroidal neovascularization (MGI Ref ID J:147328)
      • at 15 to 19 months, mice exhibit intrachoroidal neovascularization with angiographic leakage unlike wild-type mice
      • after 18 months, 3 of 13 mice exhibit choroidal neovascularization with angiographic leakage unlike in 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
  • nervous system phenotype
    • retinal photoreceptor degeneration (MGI Ref ID J:147328)
      • at 16 months
  • pigmentation phenotype
    • abnormal retinal pigment epithelium morphology (MGI Ref ID J:147328)
      • 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 (MGI Ref ID J:147328)
      • after 9 months of age, lipofuscin granules are observed in the swollen and vacuolated retinal pigmented epithelial cells unlike in wild-type mice
  • hematopoietic system phenotype
    • decreased macrophage cell number (MGI Ref ID J:147328)
      • age-dependent accumulation of macrophages in the choroids is less than in wild-type mice


The following phenotype information may relate to one or more alleles on a genetic background differing from this MMRRC strain.
Ccr2tm1Mae/Ccr2tm1Mae
        involves: 129P2/OlaHsd
  • immune system phenotype
    • abnormal chemokine secretion (MGI Ref ID J:151874)
      • there is over a 2-fold increase in Ccl2 and Ccl7 secretion by activated macrophages compared to controls
    • abnormal leukocyte migration (MGI Ref ID J:171379)
      • LPS-induced monocyte emigration is decreased compared to in similarly treated wild-type mice
    • impaired macrophage recruitment (MGI Ref ID J:151874)
      • very few macrophages are recruited in response to induced peritonitis
Ccr2tm1Mae/Ccr2tm1Mae
        involves: 129P2/OlaHsd * BALB/c
  • immune system phenotype
    • abnormal leukocyte physiology (MGI Ref ID J:162714)
      • following kidney ischemia and reperfusion, mice exhibit reduced monocyte egress from the blood into the inflamed kidney compared with similarly treated wild-type mice
      • impaired macrophage recruitment (MGI Ref ID J:162714)
        • following kidney ischemia and reperfusion
    • decreased neutrophil cell number (MGI Ref ID J:162714)
      • following kidney ischemia and reperfusion
  • homeostasis/metabolism phenotype
    • decreased circulating creatinine level (MGI Ref ID J:162714)
      • following kidney ischemia and reperfusion, plasma creatinine levels fail to increase as in similarly treated wild-type mice
    • decreased susceptibility to kidney reperfu sion injury (MGI Ref ID J:162714)
      • following kidney ischemia and reperfusion, mice fail to exhibit an increase in plasma creatinine levels and exhibit reduced renal tubular cell necrosis and neutrophil and macrophage infiltration compared with similarly treated wild-type mice
  • renal/urinary system phenotype
    • decreased susceptibility to kidney reperfusion injury (MGI Ref ID J:162714)
      • following kidney ischemia and reperfusion, mice fail to exhibit an increase in plasma creatinine levels and exhibit reduced renal tubular cell necrosis and neutrophil and macrophage infiltration compared with similarly treated wild-type mice
  • hematopoietic system phenotype
    • decreased neutrophil cell number (MGI Ref ID J:162714)
      • following kidney ischemia and reperfusion
Ccr2tm1Mae/Ccr2tm1Mae
        involves: 129P2/OlaHsd * C57BL/6J
  • growth/size phenotype
    • weight loss (MGI Ref ID J:110814)
      • mice lose ~15% body weight by day 7 of treatment, comparable to wild-type
  • immune system phenotype
    • abnormal cytokine secretion (MGI Ref ID J:110814)
      • mice expression one fifth the wild-type level of Ifng in the intestinal mucosa after day 3 and 7, while Il-4 is increased 3-fold and a 9-fold increase in Il-10 over wild-type and 4-fold greater than Ccr5-deficient mice after DSS-treatment
    • decreased CD4-positive T cell number (MGI Ref ID J:110814)
      • a decrease in number is observed at day 3 of DSS treatment
    • decreased inflammatory response (MGI Ref ID J:110814)
      • mice show significantly fewer intraabdominal adhesions than wild-type; the colons are less erythamatous and show less ulcer ation; average percentage of ulcerated tissue is less than wild-type at day 3 of treatment
    • increased B cell number (MGI Ref ID J:110814)
      • mice display an increase in B cell number in the lamina propria from 27 to 43% compared to wild-type and Ccr5-deficient mice which show a transient decrease in number at day 3 and then rebound to original values by day 7 of treatment
    • increased CD8-positive T cell number (MGI Ref ID J:110814)
      • an increase in number is observed at day 3
    • increased susceptibility to induced colitis (MGI Ref ID J:110814)
      • mice develop DSS-mediated colitis at a delayed and lower severity compared to wild-type treated mice after 7 days of treatment
  • digestive/alimentary phenotype
    • diarrhea (MGI Ref ID J:110814)
      • by day 7 of a course of dextran sodium sulfate (DSS) in drinking water, null mice develop stool diarrhea and hemoccult-positive, often bloody stool similar to wild-type; development of diarrhea and bloody stools is delayed compared to wild-type with diminished hemoccult scores on day 4 and diminished diarrhea on days 1, 3, and 4
    • increased susceptibility to induced colitis (MGI Ref ID J:110814)
      • mice develop DSS-mediated colitis at a delayed and lower severity compared to wild-type treated mice after 7 days of treatment
  • hematopoietic system phenotype
    • decreased CD4-positive T cell number (MGI Ref ID J:110814)
      • a decrease in number is observed at day 3 of DSS treatment
    • increased B cell number (MGI Ref ID J:110814)
      • mice display an increase in B cell number in the lamina propria from 27 to 43% compared to wild-type and Ccr5-deficient mice which show a transient decrease in number at day 3 and then rebound to original values by day 7 of treatment
    • increased CD8-positive T cell number (MGI Ref ID J:110814)
      • an increase in number is observed at day 3

Strain of Origin: C57BL/6J

Strain genetic background: C57BL/6J

Strain Development:

Strain Genetic Background Validation: A sample from this MMRRC strain was analyzed using the Mouse Universal Genotyping Array (MUGA) and MMRRC computational tools were used to assess the genetic background. A summary of the data can be found here.

MMRRC StrainReference StrainsGenomic makeup (Mb)
Strain Name MMRRC ID # Reference 1 Reference 2 Ref 1 Ref 2 Het Unknown
B6.129P2-Ccr2tm1Mae MMRRC:000012-UNC C57BL/6J 129P2/OlaHsd 2580 2 0 0


Research Applications

  • Inflammation
  • Role of chemokines in chronic disease development
  • Macrophage biology

Strain Origin

Donor: Nobuyo Maeda, Ph.D., University of North Carolina - Chapel Hill

Primary Reference:

Kuziel WA, Morgan SJ, Dawson TC, Griffin S, Smithies O, Ley K, Maeda N. Severe reduction in leukocyte adhesion and monocyte extravasation in mice deficient in CC chemokine receptor 2. Proc Natl Acad Sci U S A. 1997 Oct 28;94(22):12053-8. (Medline PMID: 9342361)

Colony and Husbandry Information

Special Considerations

None.

Health Status Report

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc_health@med.unc.edu.

Appearance

Coat color:

Other:

Breeding

MMRRC Breeding System:

Breeding Scheme(s):

    Generation:

    Overall Breeding Performance:

    Breeding Comments: Intra-strain mating, homos are viable

    Reproductive Statistics

    Viability and Fertility:FemaleMale
    Homozygotes are viable: Yes Yes
    Homozygotes are fertile: Yes Yes
    Heterozygotes are fertile: Yes Yes

    Age Reproductive Decline: Unknown Unknown

    Average litter size: 4-5

    Recommended wean age: 3 weeks

    Order Request Information

    Availability Level

    Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

    Conditions of Distribution [Including applicable technology transfer agreements]

    Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

    The donor or their institution limits the distribution to non-profit institutions only.

    Fees

    Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

    Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
    MMRRC Item # - Description Distribution
    Fee/unit (US $)
    Units Notes
    000012-UNC-RESUSLitter recovered from cryo-archive
    $2,022.00
    Non-Profit
    Litter Recovered litter1; additional fees for any special requests.

    1 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

    2 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

    3 An aliquot contains a sufficient number of embryos (in one or more vials and based on the transfer success rate of the MMRRC facility) to transfer to at least two recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

    To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section above). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.



    To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.



    The MMRRC is a collaborative effort, funded by grants from DPCPSI of the NIH.

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