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 agglutinin+ germinal centers and a failure in isotype switching despite normal B cell signaling in vitro.
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 donating investigator reported backcrossing this strain to C57BL/6J for at least five generations prior to sending to The Jackson Laboratory Repository (see SNP notes below).
A 32 SNP (single nucleotide polymorphism) panel analysis, with markers covering all 19 chromosomes and the X chromosome, was performed on the rederived living colony at The Jackson Laboratory Repository. This revealed 3 markers (representing one each on chromosomes 7, 12, and 19) that were not fixed for C57BL/6 allele-type (e.g.: still segregating for 129S4 allele-type markers). The marker on chromosome 12 may be fixed as homozygous for the 129S4 allele-type. These data suggest the mice may have been backcrossed to C57BL/6 for 1-2 fewer generations than reported prior to arrival at The Jackson Laboratory Repository.
|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. The expected coat color from breeding is black.
When using the B6;129S4-C3tm1Crr/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #003641 in your Materials and Methods section.