C4bp-flox Mouse

C4bp, short for C4b-binding protein, is a well-known regulator of the complement system [3,4,5]. It plays a crucial role in modulating the complement cascade, which is an essential part of the innate immune system. By binding to C4b, it helps control the activation and propagation of the complement system, thus maintaining immune homeostasis [4,5].

Screening of Neisseria gonorrhoeae strains showed that C4bp binding to gonococci via Por1A or Por1B porins contributes to serum resistance. Inhibiting C4bp binding using fAb fragments against C4bp SCR1 led to the killing of otherwise serum-resistant strains [1]. Designing chimeric proteins like C4BP-IgM enhanced complement-mediated killing of gonococci and restored susceptibility to antibiotics in resistant strains [2,8]. In the context of inflammatory bowel disease (IBD), the minor isoform C4BP(β -) and its recombinant analogue PRP6-HO7 can attenuate inflammation in DSS-induced murine colitis and in myeloid cells from IBD patients [4]. In Streptococcus pyogenes, antigenically variable M and Enn proteins recruit C4BP to the bacterial surface, enabling the bacteria to evade the immune system, and specific C4BP-binding sequence patterns have been identified [6,7].

In summary, C4bp is essential for complement regulation. Genetic models, though not specifically KO/CKO mouse models in the given references, have been used to study its role in diseases like gonorrhea, IBD, and in the immune evasion mechanism of Streptococcus pyogenes. Understanding C4bp's functions provides potential therapeutic strategies for treating these diseases, such as using chimeric proteins to enhance complement-mediated killing of bacteria or targeting C4BP(β -)-related immunomodulation for IBD treatment.