B6;129S4-C3^tm1Crr/J

Stock number: 003641
Research areas: Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

A C57BL/6J-congenic version of this strain is available as Stock No. 029661.

These knock-out mice, susceptible to infection, are useful when studying the role of C3 during immune responses.

Detailed description

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.

Development

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

Symbol: C3^tm1Crr
Name: targeted mutation 1, Michael C Carroll
MGI accession ID: MGI:1861799
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: C3
Marker name: complement component 3
Chromosome: 17
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.