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.

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