These C3 knockout mice exhibit an increased susceptibility to lethal infection by Group B streptococci, reductions in peritoneal mast cell degranulation, defects in antibody response to T cell dependent antigens and a failure in isotype switching.
Gloria Koo, Hospital for Special Surgery
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. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will 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. The mice were backcrossed to C57BL/6J for 5 generations. The mice were then crossed to CBA/J for 6 generations.
|Allele Name||targeted mutation 1, Harvey R Colten|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||C3, complement component 3|
|Strain of Origin||129/Sv|
|General Note||ES cell line = RW4 (129X1/SvJ) or D3 (129S2/SvPas).|
|Molecular Note||A genomic fragment containing 2.3 kb of the 5' flanking region and the first 105 bp of exon 1 was replaced with a neomycin selection cassette. Northern blot analysis on liver RNA derived from homozygous mice demonstrated that no detectable transcript was produced in this tissue; however, a full length transcript was detected in lung, kidney, epididymal fat tissue, spleen and heart.|
|Mutations Made By|| |
Michael Carroll, The Center for Blood Research
When maintaining a live colony, these mice can be bred as homozygotes. Donating Investigator maintained as homozygote.
When using the C3- mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #32042 in your Materials and Methods section.