Vdr-KO Mouse

Vdr, short for Vitamin D receptor, is a nuclear receptor that plays a crucial role in mediating the biological functions of 1α,25-dihydroxyvitamin D3. It is essential for the regulation of intestinal cell proliferation, barrier function, and immunity, and is involved in various pathways such as the regulation of innate and adaptive immune responses [2,3,4]. Genetic models, like gene knockout mice, have been valuable in studying its functions.

In a VDR gene knockout mouse model (VDR-/ -), when combined with a murine model of cardiac steatosis expressing DGAT1 in cardiac myocytes, there was an amplification of lipotoxic cardiomyopathy. The double-modified mice showed increased myocyte size, heart weight/body weight ratio, natriuretic peptide gene expression, interstitial fibrosis, and up-regulation of related genes, along with significant reduction in ejection fraction and fractional shortening, suggesting that VDR deficiency enhances the pathological phenotype in this cardiomyopathy model [5]. Also, in vitro studies using VDR siRNA in HK-2 cells under high glucose/transforming growth factor beta stimulation demonstrated that VDR siRNA negated the activating effects of paricalcitol on mitochondrial function, indicating VDR's role in maintaining mitochondrial function in renal tubular cells [1].

In conclusion, Vdr is a key regulator in multiple biological processes. The use of Vdr KO mouse models has revealed its importance in diseases such as cardiomyopathy and in maintaining mitochondrial function in renal tubular cells, providing insights into the underlying mechanisms and potential therapeutic targets for these disease areas.

References:

1. Chen, Hong, Zhang, Hao, Li, Ai-Mei, Zhan, Ming, Yang, Shikun. 2024. VDR regulates mitochondrial function as a protective mechanism against renal tubular cell injury in diabetic rats. In Redox biology, 70, 103062. doi:10.1016/j.redox.2024.103062. https://pubmed.ncbi.nlm.nih.gov/38320454/

2. Aggeletopoulou, Ioanna, Thomopoulos, Konstantinos, Mouzaki, Athanasia, Triantos, Christos. 2022. Vitamin D-VDR Novel Anti-Inflammatory Molecules-New Insights into Their Effects on Liver Diseases. In International journal of molecular sciences, 23, . doi:10.3390/ijms23158465. https://pubmed.ncbi.nlm.nih.gov/35955597/

3. Shang, Mei, Sun, Jun. . Vitamin D/VDR, Probiotics, and Gastrointestinal Diseases. In Current medicinal chemistry, 24, 876-887. doi:10.2174/0929867323666161202150008. https://pubmed.ncbi.nlm.nih.gov/27915988/

4. Bakke, Danika, Sun, Jun. . Ancient Nuclear Receptor VDR With New Functions: Microbiome and Inflammation. In Inflammatory bowel diseases, 24, 1149-1154. doi:10.1093/ibd/izy092. https://pubmed.ncbi.nlm.nih.gov/29718408/

5. Glenn, Denis J, Cardema, Michelle C, Gardner, David G. 2015. Amplification of lipotoxic cardiomyopathy in the VDR gene knockout mouse. In The Journal of steroid biochemistry and molecular biology, 164, 292-298. doi:10.1016/j.jsbmb.2015.09.034. https://pubmed.ncbi.nlm.nih.gov/26429397/