Mice homozygous for the Ccl3 (chemokine [C-C motif] ligand 3) (also known as macrophage inflammatory protein 1a, Mip1a or Scya3) knock-out mutation show multiple deficiencies including clearance of influenza virus, bone remodeling during orthodontic tooth movement, liver fibrosis after treatments to induce fibrosis, metastasis with melanoma (but not with renal cell carcinoma where intra-tumoral neovascularization is attenuated). These mice can be useful in studies of chemokine receptors in inflammatory diseases.
Dr. Oliver Smithies, University of North Carolina at Chapel Hill
Mice homozygous for the Ccl3 (chemokine [C-C motif] ligand 3) (also known as macrophage inflammatory protein 1a, Mip1a or Scya3) knock-out mutation are viable and fertile. Homozygous mutant mice are resistant to Coxsakievirus-induced myocarditis. Mutant mice infected with influenza virus show reduced pneumonitis and delayed clearance of virus. There are no overt hematopoietic abnormalities. Bone remodeling induced by mechanical loading during orthodontic tooth movement was significantly decreased in Ccl3tm1Unc mice. Compared to wild-type mice liver fibrosis was reduced upon treatment with either carbon tetrachloride or methionine- and choline-deficient diets to induce fibrosis. Melanoma growth is augmented and lung metastasis is enhanced in these knock-out mice. With renal cell carcinoma, however, the number of metastasis foci in the lung is reduced, and intra-tumoral neovascularization, an indispensable process for metastasis, is attenuated in these gene-deficient mice. These mice can be useful in studies of chemokine receptors in inflammatory diseases.
A neomycin selection cassette was used to delete a region including 300 nucleotides of the 5' un-translated region, all of exon 1, and a portion of exon 2. Correctly targeted 129 ES cells were injected into C57BL/6J blastocysts.
|Allele Name||targeted mutation 1, University of North Carolina|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||CCL3-; MIP-1alpha -; Scya3 -; Scya3tm1Coo|
|Gene Symbol and Name||Ccl3, chemokine (C-C motif) ligand 3|
|Gene Synonym(s)||464.2; AI323804; CCL3; D17S1718; G0S19-1; G0S19-2; LD78; LD78ALPHA; LD78BETA; LD78alpha; MIP-1 alpha; MIP-1-alpha; MIP-1a; MIP-1alpha; MIP1-(a); MIP1-alpha; MIP1A; Mip1a; Mip1a; SCYA3; SCYA3L; SCYA3L1; Scya3; Scya3; expressed sequence AI323804; macrophage inflammatory protein-1 alpha; macrophage inflammatory protein-1alpha; small inducible cytokine A3|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||A neomycin selection cassette was used to delete a region including 300 nucleotides of the 5' untranslated region, all of exon 1, and a portion of exon 2. An absence of transcript was observed via Northern blot analysis of total mRNA derived from bone marrow macrophages isolated from homozygous mutant animals.|
|Mutations Made By|| |
Dr. Oliver Smithies, University of North Carolina at Chapel Hill
|Please inquire about possible genotypes.|
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