These partially humanized C1q mice are useful when studying the mechanisms of C1q activation and contribution to human health and disease.
Andrea J. Tenner, University of California, Irvine
These mice contain four mutations (A13, P14, N16, P20) in the complement component 1, q subcomponent, alpha polypeptide (C1qa) gene, designed to mimic the corresponding sequence from human A chain (E13, A14, R16, R20). 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 lack arginine residues in the C1q A chain N-terminal collagen-like region, present in humans which are present in humans and thought to enable CCP activation by some non immune complex activators. These mice contain mutations that facilitate binding of molecules like beta-amyloid fibrils (fAβ) to C1q. While these mice did not show any differences in C1 activation by beta amyloid or DNA, these paritially humanized C1q mice should be useful when studying the mechanisms of C1q activation and contribution to human health and disease. Homozygotes are viable and fertile.
A targeting construct was made to replace four amino acids of the mouse complement component 1, q subcomponent, alpha polypeptide (C1qa) sequence (A13, P14, N16, P20) with human sequence (E13, A14, R16, R20). A loxP-flanked neo cassette was inserted downstream of exon 1. This targeting construct was electroporated into 129P2/OlaHsd-derived E14TG2a embryonic stem (ES) cell line. Correctly targeted ES cells were transiently transfected with a Cre expression plasmid to delete the neo cassette. Resulting ES cells were injected into C57BL/6J blastocysts. The resulting chimeric males were bred to C57BL/6J females. These mice were bred to C57BL/6J mice (Stock No. 000664) for at least 6 generations.
|Allele Name||targeted mutation 1.1, Andrea J Tenner|
|Allele Type||Targeted (Humanized sequence)|
|Gene Symbol and Name||C1qa, complement component 1, q subcomponent, alpha polypeptide|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||Four amino acids within the exon 1 of the mouse sequence were converted to the corresponding human sequence and introduced by targeted homologous recombination with loxP flanked neo cassette place in intron 1. The neo cassette was removed either by crossing with deleter cre expressing strain or by transient transfection with cre.|
When maintaining a live colony, homozygous mice may be bred together.
When using the humanized C1q A chain mouse strain in a publication, please cite the originating article(s) and include JAX stock #023726 in your Materials and Methods section.