B6(SJL)-C1qa^{tm1c(EUCOMM)Wtsi}/TennJ

Stock number: 031261
Product name: C1qa^FL
Research areas: Immunology, Inflammation and Autoimmunity Research, Neurobiology Research, Research Tools

Description

C1qa^FL floxed mice have exon 3 of the complement component 1, q subcomponent, alpha polypeptide (C1qa) gene, floxed, making these mice useful for studying the mechanisms of C1q activation and contribution to human health and disease.

Detailed description

C1qa^FL floxed mice have loxP sites flanking exon 3 of the complement component 1, q subcomponent, alpha polypeptide (C1qa) gene. C1q, a macromolecule composed of 6 each of A, B, and C chains, is a component of the classical complement pathway (CCP) which can be activated by immune complexes (via interaction with multiple C1q globular domains) as well as molecules containing specifically spaced negative charges. Excessive or unregulated complement activation can contribute to the pathogenesis of diseases such as Alzheimer's disease. Mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 3 deleted in the cre-expressing tissues.

Development

The L1L2_Bact_P cassette was inserted at a position on Chromosome 4 upstream of exon 3 of the complement component 1, q subcomponent, alpha polypeptide (C1qa) gene. The cassette is composed of a frt site followed by lacZ sequence and a loxP site. This first loxP site is followed by neomycin under the control of the human beta-actin promoter, SV40 polyA, a second frt site and a second loxP site. A third loxP site was inserted in the 3’ untranslated region of exon 3. The construct, clone EPD0618_1_B03, was introduced into C57BL/6N-A^tm1Brd-derived JM8A3.N1 embryonic stem (ES) cells, and correctly targeted ES cells were injected into B6(Cg)- Tyr^c-2J/J (Stock No. 58) blastocysts. The resulting chimeric males were bred to C57BL/6NJ (Stock No. 005304) mice. Dr. Andrea Tenner (University of California, Irvine) obtained some of these mice and bred them to B6.Cg-Tg(ACTFLPe)9205Dym/J mice (Stock No. 005703) to remove the frt-flanked lacZ sequence and neomycin cassette. Resulting C1qa^FL offspring were bred to C57BL/6J mice to remove the flpe-expressing transgene, and were maintained on a C57BL/6J background.

Allele

Symbol: C1qa^{tm1c(EUCOMM)Wtsi}
Name: targeted mutation 1c, Wellcome Trust Sanger Institute
MGI accession ID: MGI:6108260
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: C1qa^FL
Marker symbol: C1qa
Marker name: complement component 1, q subcomponent, alpha polypeptide
Marker synonyms: Adic; C1q; C1QD1
Chromosome: 4
Strain of origin: C57BL/6N-A^tm1Brd
Molecular note: The L1L2_Bact_P cassette was inserted at a position on Chromosome 4 upstream of exon 3 of the gene. The cassette is composed of an FRT site followed by lacZ sequence and a loxP site. This first loxP site is followed by neomycin resistance gene under the control of the human beta-actin promoter, SV40 polyA, a second FRT site and a second loxP site. A third loxP site was inserted in the 3' untranslated region of exon 3. Flp-mediated recombination removed the FRT-flanked lacZ and neo cassette.