Mouse Strains

B6.Cg-Ccl2tm1.1Pame/J Mouse Strain

By October 12, 2019 November 14th, 2019 No Comments

Overview

B6.Cg-Ccl2tm1.1Pame/J, also known as Ccl2-RFPflox, is a genetically modified strain of mouse that contains LoxP sites flanking the gene Ccl2, allowing for easy modification and removal of that gene. It is mainly used in immunology research.[1]

History

B6.Cg-Ccl2tm1.1Pame/J is ultimately derived from the highly popular strain C57BL/6J, via the related B6(Cg)-Tyrc-2J/J.

A vector was electroporated into B6(Cg)-Tyrc-2J/J embryonic stem cells which were injected into the embryos of normal C57BL/6J mice to create chimeric offspring. Offspring heterozygous for Ccl2 were then crossed with B6.Cg-Tg(ACTFLPe)9205Dym/J, and afterwards, crossed with one another to create homozygotes.

Finally, the homozygotes were backcrossed with normal C57BL/6J for ten generations.[1]

Physical Characteristics

B6.Cg-Ccl2tm1.1Pame/J appear like normal C57BL/6J mice and so have black fur.[2] One major difference is that red fluorescence, due to the protein mcherry is seen in all the cells of these mice that express the gene Ccl2.[2]

Behavioral Characteristics & Handling

No information specific to the handling or behavior of this strain could be found. However, since these mice are near identical to C57BL/6J, one would expect the same handling advice to apply to both. Research shows that C57BL/6J is a docile strain that is easy to handle, although not as docile as BALB/cJ.[3]

It is also worth taking additional caution with mice of this strain who have had the Ccl2 gene excised, since their reduced immune function makes them more liable to infection. Researchers should wear gloves and masks when handling these mice, and house them under sterile conditions isolated from mice of other strains.

Health Characteristics

The gene Ccl2 encodes for the cytokine (immune system signaling molecule) chemokine C-C motif ligand 2, also known as monocyte chemoattractant protein 1 (MCP1).[4] The major health characteristics of this strain result when the Ccl2 gene is removed, otherwise it exhibits the same health characteristics as a normal mouse.

Ccl2 resides in the cell membrane of a number of different immune cells, most prominently dendritic cells, macrophages and monocytes. This cytokine is involved in attracting immune cells to sites of interests and also plays a role in the formation of granulomas. It is expressed mainly inside the bones as well as in various regions of the brain.[5]

When Ccl2 is knocked out, monocytes are no longer able to travel out from the bone marrow to the bloodstream in order to reach sites of infection. As a result, the affected mice show a greater susceptibility to infection. Otherwise, they do not show any significant health abnormalities and are both viable and fertile.[1]

Major Experimental Uses

Since Ccl2 is primarily involved with immune system regulation, this strain will be of interest mainly to researchers interested in studying immune function and immune disorders, especially issues around the migration of monocytes from bone marrow.

In humans, the Ccl2 gene is associated with a number of different immune disorders including arthritis, psoriasis, kidney disease, atherosclerosis, insulin resistance and neuroinflammation.[6][7][8] Hence, researchers interested in investigating any of these diseases could also find a use for B6.Cg-Ccl2tm1.1Pame/J.

Since this strain resembles C57BL/6J mice in all except the increased ease of knocking out its Ccl2 gene, researchers interested in areas of study other than immunology would be advised to opt for the normal C57BL/6J.

References

  1. 016849 – B6.Cg-Ccl2/J. 2019. 016849 – B6.Cg-Ccl2/J. [ONLINE] Available at: https://www.jax.org/strain/016849. [Accessed 11 September 2019].
  2. 000664 – C57BL/6J. 2019. 000664 – C57BL/6J. [ONLINE] Available at: https://www.jax.org/strain/000664. [Accessed 11 September 2019].
  3. Wahlsten, D. Metten, P. Crabbe, JC. 2003. A rating scale for the wildness and ease of handling laboratory mice: results for 21 inbred strains tested in two laboratories. Genes, Brain and Behavior. 2; 71-79.
  4. GeneCards Human Gene Database. 2019. CCL2 Gene – GeneCards | CCL2 Protein | CCL2 Antibody. [ONLINE] Available at: https://www.genecards.org/cgi-bin/carddisp.pl?gene=CCL2. [Accessed 11 September 2019].
  5. Deshmane, S. L., Kremlev, S., Amini, S., & Sawaya, B. E. 2009. Monocyte chemoattractant protein-1 (MCP-1): an overview. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research. 29(6), 313–326.
  6. Xia M, Sui Z. 2009. Recent developments in CCR2 antagonists. Expert Opinion on Therapeutic Patents. 19 (3): 295–303.
  7. Lloyd CM, Minto AW, Dorf ME, Proudfoot A, Wells TN, Salant DJ, Gutierrez-Ramos JC. 1997. RANTES and monocyte chemoattractant protein-1 (MCP-1) play an important role in the inflammatory phase of crescentic nephritis, but only MCP-1 is involved in crescent formation and interstitial fibrosis. The Journal of Experimental Medicine. 185 (7): 1371–80.
  8. Gerard C, Rollins BJ. 2001. Chemokines and disease. Nature Immunology. 2 (2): 108–15.

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