C6 MOA: C6 participates in the initiation of membrane attack complex (MAC) assembly.

•Gene Information: This gene encodes component C6 of the complement system. C6 serves as the foundational scaffold of the terminal complement complex by specifically binding to C5b and recruiting C7/C8/C9 to assemble the membrane attack complex (MAC) for target cell lysis.

•Protein Expression: It is constitutively expressed mainly in the liver under physiological conditions to maintain the complement level in blood.

•Signaling Pathway: C6 participates in all the pathways of complement, serving as a key component in the complement cascade activation pathway.

•Application : This mouse model can be utilized to evaluate the efficacy of both monoclonal antibodies (mAbs) and nucleic acid therapeutics (RNAi / ASO).

Key Advantages

Complete Human protein：The full human C6 gene was knock in humanized mice .

Normal Phenotypes：No obvious abnormal phenotypes have been observed during the feeding and maintenance of these mice.

Suitable for small nucleic acid drugs：This mouse carries the human 3'UTR sequence.

Key Applications

Efficacy & Safety Evaluation:Supports efficacy and safety assessment of anti-hC6 antibodies and small nucleic acid drugs.

Novel Therapeutic Screening:Support the discovery, screening, and optimization of new treatment strategies, leveraging a relevant humanized models for translational research.

Gene targeting strategy for B-hC6 mice.

1.The exons 1~18 of mouse C6 gene were replaced by human exons 1~18 (with 3’UTR) that encode the whole molecule in B-hC6 mice.

2.The promoter and 5’UTR region of the mouse gene are retained.

3.The human C6 protein expression is driven by endogenous mouse C6 promoter.

Human C6 mRNA was detectable only in homozygous B-hC6 mice but not in wild-type mice.

Species specific analysis of C6 gene expression in wild-type C57BL/6JNifdc mice and homozygous humanized B-hC6 mice by RT-PCR. Liver was collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hC6 mice (H/H). Mouse C6 mRNA was detectable in wild-type C57BL/6JNifdc mice. Human C6 mRNA was exclusively detectable in homozygous B-hC6 mice but not in wild-type C57BL/6 mice.

Human C6 was detected in homozygous  B-hC6 mice, but not in wild-type mice.

Strain specific C6 expression analysis in wild-type C57BL/6JNifdc mice and homozygous humanized B-hC6 mice by ELISA.

Serum was collected from wild-type C57BL/6JNifdc mice (+/+) (male, n=3, 8-week-old) and homozygous B-hC6 mice (H/H) (male, n=3, 8-week-old). Expression level of human C6 were analyzed by ELISA (human C6 ELISA kit: Novus Biologicals, NBP2-60558). Human C6 was exclusively detectable in homozygous B-hC6 mice (n=3). Values are expressed as mean ± SEM.