Dnase2a, also known as DNase II, is a lysosomal nuclease. Its essential function is to degrade DNA, participating in multiple biological processes. It is involved in the phagolysosomal degradation of apoptotic cell DNA, and the nucleotides derived from this hydrolysis can activate the DNA-PKcs-mTORC2/Rictor pathway, promoting non-inflammatory macrophage proliferation [1]. It also plays a role in the clearance of damaged nuclear DNA in non-phagocytic cells, with this process requiring nuclear export and autophagy-mediated delivery of DNA to lysosomes [2].

In gene knockout mouse models, Dnase2a deficiency leads to elevated levels of undegraded DNA in cells. In non-phagocytic cells, this excess DNA comes from damaged nuclear DNA. The accumulated DNA can induce inflammation via the Sting cytosolic DNA-sensing pathway [2]. In atherosclerosis regression, silencing macrophage Dnase2a blocks efferocyte proliferation, apoptotic cell clearance, and plaque stabilization [1]. In definitive erythropoiesis, Dnase2a KO mice suffer from severe anemia and die in utero, as it is crucial for digesting the DNA of extruded nuclei of red blood cells during maturation [3].

In conclusion, Dnase2a is vital for DNA degradation in various biological contexts. Its deficiency in KO mouse models reveals its importance in processes like apoptotic cell clearance, macrophage proliferation, and erythropoiesis, with implications for diseases such as atherosclerosis and anemia. Understanding Dnase2a through these models provides insights into the underlying mechanisms of these biological processes and disease conditions.