Bdkrb1-KO Mouse

Bdkrb1, the gene encoding the bradykinin B1 receptor, is involved in the kallikrein-kinin system. Bradykinin, upon binding to BDKRB1, can prompt calcium influx, and this receptor is associated with multiple biological pathways including those related to cell migration, inflammation, and vascular regulation. Genetic models, such as gene knockout mice, are valuable for studying its functions [1,3,4,5].

In a rat model of Wolfram syndrome, Bdkrb1 expression was drastically downregulated at an early stage, suggesting that Wfs1 deficiency might disturb the normal functioning of the kallikrein-kinin system [2]. In mice lacking Bdkrb1 (Bdkrb1(-/-)), increased bone loss and IL-17 secretion were observed in a ligature-induced experimental periodontitis model, indicating Bdkrb1's role in periodontitis pathogenesis [4]. Also, Bdkrb1-deficient C57BL/6 mice immunized with a myelin oligodendrocyte glycoprotein fragment showed more severe experimental autoimmune encephalomyelitis with enhanced CNS-immune cell infiltration, suggesting that Bdkrb1 limits encephalitogenic T lymphocyte recruitment to the CNS [5].

In conclusion, Bdkrb1 plays essential roles in inflammation, bone remodeling, and regulation of immune cell infiltration into the CNS. Studies using Bdkrb1 KO mouse models have provided insights into its functions in diseases like periodontitis and multiple sclerosis-related CNS inflammation, contributing to a better understanding of disease mechanisms and potential therapeutic targets.

References:

1. Sun, Ding-Ping, Lee, Yuan-Wen, Chen, Jui-Tai, Lin, Yung-Wei, Chen, Ruei-Ming. 2020. The Bradykinin-BDKRB1 Axis Regulates Aquaporin 4 Gene Expression and Consequential Migration and Invasion of Malignant Glioblastoma Cells via a Ca2+-MEK1-ERK1/2-NF-κB Mechanism. In Cancers, 12, . doi:10.3390/cancers12030667. https://pubmed.ncbi.nlm.nih.gov/32182968/

2. Punapart, Marite, Seppa, Kadri, Jagomäe, Toomas, Vasar, Eero, Plaas, Mario. 2021. The Expression of RAAS Key Receptors, Agtr2 and Bdkrb1, Is Downregulated at an Early Stage in a Rat Model of Wolfram Syndrome. In Genes, 12, . doi:10.3390/genes12111717. https://pubmed.ncbi.nlm.nih.gov/34828323/

3. Angers, Martin, Drouin, Régen, Bachvarova, Magdalena, Usheva, Anny, Bachvarov, Dimcho. . In vivo DNase I-mediated footprinting analysis along the human bradykinin B1 receptor (BDKRB1) gene promoter: evidence for cell-specific regulation. In The Biochemical journal, 389, 37-46. doi:. https://pubmed.ncbi.nlm.nih.gov/15705059/

4. Gonçalves-Zillo, Thais Oliveira, Pugliese, Lívia Souza, Sales, Vicência Micheline Toledo, Monteiro, Ana Carolina, Pesquero, João Bosco. 2013. Increased bone loss and amount of osteoclasts in kinin B1 receptor knockout mice. In Journal of clinical periodontology, 40, 653-60. doi:10.1111/jcpe.12097. https://pubmed.ncbi.nlm.nih.gov/23534940/

5. Schulze-Topphoff, Ulf, Prat, Alexandre, Prozorovski, Timour, Aktas, Orhan, Zipp, Frauke. 2009. Activation of kinin receptor B1 limits encephalitogenic T lymphocyte recruitment to the central nervous system. In Nature medicine, 15, 788-93. doi:10.1038/nm.1980. https://pubmed.ncbi.nlm.nih.gov/19561616/