Bdkrb2-KO Mouse

Bdkrb2, encoding the bradykinin B2 receptor, plays a crucial role in regulating nitric oxide production to control vasodilatation [3]. It is also involved in the epithelial-to-mesenchymal transition (EMT) process, and its expression is associated with the aggressiveness of gliomas [2]. Additionally, it may be related to genetic factors in athletic performance [4,5,6]. Genetic models can help in understanding its functions and gene-environment interactions.

In the developing kidney, Bdkrb2(-/-) embryos exposed to gestational salt stress develop renal dysgenesis. The underlying mechanism involves p53 stabilization, apoptosis, and repression of terminal epithelial differentiation. There is a functional cross-talk between p53 and BdkrB2, where BdkrB2 is a target for p53-mediated transcriptional activation, and BdkrB2 inactivation upregulates Chk1 levels, potentiating p53 phosphorylation on Ser23 by Chk1, a step in renal dysgenesis in salt-stressed BdkrB2(-/-) mutant mice [1].

In conclusion, Bdkrb2 is essential for vasodilatation regulation and is involved in EMT in gliomas and athletic performance-related genetic factors. Mouse models with Bdkrb2 knockout have revealed its role in renal development and the importance of its interaction with p53 in the context of renal dysgenesis. These findings contribute to understanding diseases related to kidney development and potentially other pathological conditions associated with Bdkrb2 dysregulation [1].

References:

1. El-Dahr, Samir S, Saifudeen, Zubaida. . Interactions between BdkrB2 and p53 genes in the developing kidney. In Biological chemistry, 394, 347-51. doi:10.1515/hsz-2012-0281. https://pubmed.ncbi.nlm.nih.gov/23152407/

2. Yang, Ying, Wang, Jin, Shi, Fei, Xu, Shihai, Lv, Wen. 2021. BDKRB2 is a novel EMT-related biomarker and predicts poor survival in glioma. In Aging, 13, 7499-7516. doi:10.18632/aging.202614. https://pubmed.ncbi.nlm.nih.gov/33686021/

3. Niu, Jingjing, Song, Weihao, Li, Rui, Qi, Jie, He, Yan. 2021. The Bdkrb2 gene family provides a novel view of viviparity adaptation in Sebastes schlegelii. In BMC ecology and evolution, 21, 44. doi:10.1186/s12862-021-01774-0. https://pubmed.ncbi.nlm.nih.gov/33731008/

4. İpekoğlu, Gökhan, Apaydın, Necdet, Çetin, Tuğba, Civelek, Güngör, Sakar, Mert. 2024. Examining the relationship between genetic polymorphisms (BDKRB2, GNB3, HIF1A, MCT1, NOS3) and endurance athlete status. In European journal of applied physiology, 124, 1943-1958. doi:10.1007/s00421-024-05498-z. https://pubmed.ncbi.nlm.nih.gov/38753016/

5. Grenda, A, Leońska-Duniec, A, Cięszczyk, P, Zmijewski, P. 2014. Bdkrb2 gene -9/+9 polymorphism and swimming performance. In Biology of sport, 31, 109-13. doi:10.5604/20831862.1096047. https://pubmed.ncbi.nlm.nih.gov/24899774/

6. Shrestha, Alvin, Bashir, Tufail, Achison, Marcus, Witham, Miles D, Kemp, Paul R. 2024. Association of bradykinin receptor 2 (BDKRB2) variants with physical performance and muscle mass: Findings from the LACE sarcopenia trial. In PloS one, 19, e0307268. doi:10.1371/journal.pone.0307268. https://pubmed.ncbi.nlm.nih.gov/39093910/