Gdf2-KO Mouse

Gdf2, also known as Bmp9, encodes bone morphogenetic protein 9. It plays a pivotal role in pulmonary vascular regulation and is involved in the transforming growth factor-beta signaling pathway [1, 4-6, 9, 10]. Gdf2 and Bmp10, which are closely related, are important for maintaining liver cell-cell crosstalk, with hepatic stellate cells being the major source of GDF2 and BMP10 in the liver. They promote the differentiation of Kupffer cells and endothelial cells and maintain their identity, and also regulate hepatocyte iron metabolism and metabolic zonation [1].

In a study generating mice with conditional deletion of Gdf2 and Bmp10 in different liver cell types, it was found that deletion led to up-regulation of Pdgfb in Kupffer cells and endothelial cells, ultimately causing hepatic stellate cells activation and liver fibrosis. Also, angiocrine factors in endothelial cells were decreased, resulting in liver iron overload and disruption of hepatocyte zonation, revealing the crucial role of Gdf2 in liver health maintenance [1].

In conclusion, Gdf2 is essential for pulmonary vascular regulation and liver cell-cell crosstalk. The conditional knockout mouse models have demonstrated its significance in liver-related biological processes. In the context of diseases, Gdf2 variants are associated with pulmonary arterial hypertension and hereditary hemorrhagic telangiectasia, highlighting its importance in understanding the pathophysiology of these conditions [1-2, 4-6, 9-10].

References:

1. Zhao, Dianyuan, Huang, Ziwei, Li, Xiaoyu, Hao, Yanan, Tang, Li. 2024. GDF2 and BMP10 coordinate liver cellular crosstalk to maintain liver health. In eLife, 13, . doi:10.7554/eLife.95811. https://pubmed.ncbi.nlm.nih.gov/39453386/