Cfhr1-KO Mouse

Cfhr1, or Complement Factor H-related protein 1, is associated with the complement system, a crucial part of the immune response. It plays a role in regulating the complement alternative pathway, which is involved in host defense against pathogens and in maintaining immune homeostasis [2].

In a sepsis-induced acute lung injury (ALI) model using Cfhr1-knockout mice, deletion of Cfhr1 led to excessive activation of the complement alternative pathway. These Cfhr1-knockout mice had increased C3a formation in lung tissues after Staphylococcus aureus infection, indicating enhanced terminal complement pathway activation. They also had higher bacterial colony counts in the lungs, suggesting impaired S. aureus clearance, thus exacerbating S. aureus-induced sepsis and ALI [1]. In addition, sequence and copy number variations in the CFHR-Factor H gene cluster including Cfhr1 are linked to kidney diseases such as atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy [2]. A study also found that Cfhr1 gene deletion-associated thrombotic microangiopathy may be triggered by Shiga toxin [3]. And in a systemic lupus erythematosus patient with thrombotic microangiopathy, genetic analysis showed a large heterozygous deletion encompassing the entire Cfhr1 and Cfhr3 [4].

In conclusion, Cfhr1 is important for regulating the complement alternative pathway. Studies using Cfhr1 knockout mouse models have revealed its role in various disease conditions, including sepsis-induced ALI, kidney diseases, and thrombotic microangiopathy. Understanding the function of Cfhr1 provides insights into the pathogenesis of these diseases and may offer potential therapeutic targets.

References:

1. Li, Rubo, Fan, Chaonan, Liu, Gang, Duan, Hongnian, Qian, Suyun. 2024. Cfhr1 gene deficiency exacerbates Staphylococcus aureus-induced sepsis and acute lung injury through complement alternative pathway hyperactivation. In Biochemical and biophysical research communications, 737, 150466. doi:10.1016/j.bbrc.2024.150466. https://pubmed.ncbi.nlm.nih.gov/39128222/

2. Zipfel, Peter F, Wiech, Thorsten, Stea, Emma D, Skerka, Christine. 2020. CFHR Gene Variations Provide Insights in the Pathogenesis of the Kidney Diseases Atypical Hemolytic Uremic Syndrome and C3 Glomerulopathy. In Journal of the American Society of Nephrology : JASN, 31, 241-256. doi:10.1681/ASN.2019050515. https://pubmed.ncbi.nlm.nih.gov/31980588/

3. Nalluru, Swarna Sri, Sridharan, Meera, Go, Ronald S, Said, Samar, Marshall, Ariela L. 2018. Shiga Toxin as a Potential Trigger of CFHR1 Deletion-Associated Thrombotic Microangiopathy. In The American journal of the medical sciences, 356, 492-498. doi:10.1016/j.amjms.2018.05.012. https://pubmed.ncbi.nlm.nih.gov/30177262/

4. de Holanda, Maria Izabel, Pôrto, Luis Cristóvão, Wagner, Teresa, Christiani, Luis Fernando, Palma, Lilian M P. 2017. Use of eculizumab in a systemic lupus erythemathosus patient presenting thrombotic microangiopathy and heterozygous deletion in CFHR1-CFHR3. A case report and systematic review. In Clinical rheumatology, 36, 2859-2867. doi:10.1007/s10067-017-3823-2. https://pubmed.ncbi.nlm.nih.gov/28905254/