Mice homozygous for the C3 (complement component C3) targeted mutation are viable and fertile. Homozygous mutants exhibit an increased susceptibility to lethal infection by Group B streptococci. Reductions in peritoneal mast cell degranulation, production of tumor necrosis factor alpha, neutrophil infiltration and bacterial clearance have also been reported in these mice. Homozygotes also demonstrate a profound defect in antibody response to T cell dependent antigens. They show a diminished level of peanut agglutin+ germinal centers and a failure in isotype switching despite normal B cell signalling in vitro.
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. It should be noted that the phenotype of these congenic mice could vary from that originally described on a mixed genetic background. We may modify the strain description if necessary as published results become available.
The C3 gene is disrupted by PGK/Neo cassette. Approximately 600 nt of the gene are deleted. A portion of these nts (nt 1850-2214; AA 620-741, pro-C3 numbering) fall within the coding region. The targeting construct was transfected into 129S4/SvJae derived J1 ES cells. Successful transfectants were injected into 3.5 day old C57BL/6 blastocysts which were then implanted into the uterus of pseudopregnant females. Male chimeric mice were bred with C57BL/6 females, and subsequently the mice were backcrossed to C57BL/6 mice for 1-2 more generations. Mice on this mixed background (Stock No. 003641) were further backcrossed to C57BL/6J mice for many generations using a marker-assisted, speed congenic approach to generate this congenic strain, Stock No. 029661.
|Allele Name||targeted mutation 1, Michael C Carroll|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||C3tm1Crr; C3-; mC3-|
|Gene Symbol and Name||C3, complement component 3|
|Strain of Origin||129S4/SvJae|
|Molecular Note||Insertion of a PGK-neomycin resistance cassette into an exon of the C3 gene deleted sequences that code for the C-terminal region of the beta chain and the N-terminal region of the alpha chain, including the site for processing the pro-C3 molecule. ELISA testing did not detect C3 protein in serum of homozygous mutant mice. A C3 hemolytic assay did not detect functional C3 activity.|
|Mutations Made By|| |
Michael Carroll, The Center for Blood Research
When maintaining a live colony, homozygous mice may be bred together.
When using the C3 KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #029661 in your Materials and Methods section.