B6.129S4-C4b^tm1Crr/J

Stock number: 003643
Product name: C4 KO
Research areas: Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

These C4b knock-out mice exhibit an increased susceptibility to lethal infection by Group B streptococci.

Detailed description

Mice homozygous for the C4 (complement component C4) targeted mutation are viable and fertile. Homozygous mutants exhibit an increased susceptibility to lethal infection by Group B streptococci(GBS). C4 homozygous mutants show a similar susceptibility to GBS lethal infection as do C3 null mice, suggesting that the classical, and not alternative, pathway is primarily involved in antibody-independent humoral immunity to GBS. 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.

Development

The C4 locus was disrupted by the insertion of a PGK/Neo cassette. This resulted in the deletion of exons 23 to 29 (987 ntds). The targeting construct was transfected into J1 ES cells and 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. Mice were backcrossed to C57BL/6J until N5.

Allele

Symbol: C4b^tm1Crr
Name: targeted mutation 1, Michael C Carroll
MGI accession ID: MGI:1889070
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: C4b
Marker name: complement component 4B (Chido blood group)
Chromosome: 17
Strain of origin: 129S4/SvJae
Molecular note: A genomic fragment corresponding to 987 nucleotides of coding sequence (exons 23-29) was replaced with a neomycin selection cassette. ELISA assays on serum derived from homozygous mice demonstrated that no detectable protein is produced from this allele.