B6-hC3 Mice

Catalog Number: I001135

Strain Name: C57BL/6JCya-C3tm1(hC3)/Cya

Genetic Background: C57BL/6JCya

One of Cyagen's HUGO-GT™ (Humanized Genomic Ortholog for Gene Therapy) Strains

 

Strain Description

Complement component C3 plays a central role in activating the complement system and is the most abundant complement protein in human plasma, primarily synthesized in the liver. As part of the innate immune system, the complement system is activated during tissue damage and pathogen invasion, playing a crucial role in the inflammatory response, host homeostasis, and pathogen defense. The complement cascade is activated through the classical pathway, alternative pathway, and lectin pathway, all of which generate C3 convertase, which cleaves C3 into C3a and C3b. C3a is a potent anaphylatoxin with pro-inflammatory activity, while C3b is a regulator that induces C5 cleavage, thereby participating in the dissolution and clearance of immune complexes. Mutations in this gene are associated with atypical hemolytic uremic syndrome (aHUS) and age-related macular degeneration (AMD). Deficiencies in C3 and C3-derived peptides can lead to autoimmune diseases (such as rheumatoid arthritis, systemic lupus erythematosus, and vasculitis) and make individuals susceptible to recurrent respiratory infections and infections caused by encapsulated organisms. Conversely, excessive activation of C3 and related complement components is associated with kidney diseases (immune complex glomerulonephritis, hemolytic uremic syndrome, lupus nephritis, membranous nephropathy, and immune-mediated nephropathy) [1-2].

The B6-hC3 mouse is a mouse C3 humanized model created by replacing the mouse C3 gene with the human C3 gene using gene-editing technology. The humanized regions include the 5’UTR and 3’UTR. Under natural breeding conditions, homozygous B6-hC3 mice exhibit mortality around 10 weeks of age, and it has been observed that heterozygous mice also experience mortality. Additionally, based on the innovative TurboKnockout technology combined with BAC recombination developed by Cyagen Biosciences, customized services are available for different mutations to meet the experimental needs of researchers studying complement-mediated diseases.

Strain Strategy


Figure 1. Gene editing strategy of B6-hC3 mice. The sequences from ~6.6 kb upstream of exon 1 to the TGA stop codon of mouse C3 were replaced with the sequences from ~9 kb upstream of exon 1 to ~1.5 kb downstream of exon 41 of human C3.

Application

  • Preclinical research on C3-targeted drugs;
  • Research in immunotherapy, oncology, etc.

 

Validation Data

1. ELISA


Figure 2. Expression of human C3 protein in the serum of wild-type mice (WT) and B6-hC3 mice. ELISA results indicate significant expression of human C3 protein in the serum of homozygous males (hC3-Ho-♂), homozygous females (hC3-Ho-♀), and heterozygous females (hC3-Het-♀) B6-hC3 mice. (hC3-Ho&WT: 5w; hC3-Het: 7w; n=5; data presented as mean ± SD)

 

References
[1]Delanghe JR, Speeckaert R, Speeckaert MM. Complement C3 and its polymorphism: biological and clinical consequences. Pathology. 2014 Jan;46(1):1-10.
[2]Yates JR, Sepp T, Matharu BK, Khan JC, Thurlby DA, Shahid H, Clayton DG, Hayward C, Morgan J, Wright AF, Armbrecht AM, Dhillon B, Deary IJ, Redmond E, Bird AC, Moore AT; Genetic Factors in AMD Study Group. Complement C3 variant and the risk of age-related macular degeneration. N Engl J Med. 2007 Aug 9;357(6):553-61.