Bmp10-KO Mouse

Bmp10, a member of the bone morphogenetic protein (BMP) family and the transforming growth factor β (TGFβ) superfamily, plays crucial roles in various biological processes. It is a key regulator in vascular development and cardiogenesis, and is involved in the ALK1-related signaling pathway, which is linked to hereditary hemorrhagic telangiectasia (HHT) and pulmonary arterial hypertension (PAH) [1,3,4]. Bmp10 also contributes to the regulation of iron homeostasis, maintaining cardiac function [2].

In gene-knockout studies, combined loss of zebrafish bmp10 and bmp10-like leads to embryonic lethal cranial arteriovenous malformations (AVMs) similar to acvrl1 mutants, and bmp10 mutants show blood vessel abnormalities, heart dysmorphology, and premature death [4]. In Bmp10-inducible knockout (iKO) mice, AVMs are present in the developing retina, postnatal brain, and adult wounded skin, with increased proliferation and size of endothelial cells in AVM vessels [3]. In zebrafish, mutation of bmp10 results in severe anemia and cardiac hypertrophy due to iron homeostasis dysregulation [2].

In conclusion, Bmp10 is essential for vascular development and maintenance, as well as for regulating iron homeostasis in the heart. Gene-knockout mouse and zebrafish models have significantly contributed to understanding its role in diseases like HHT and iron-related cardiomyopathy, highlighting its potential as a therapeutic target in these disease areas.