Slc25a38-flox Mouse

Slc25a38, a mitochondrial solute carrier, is crucial for mitochondrial functions. It acts as a mitochondrial glycine carrier and is involved in pathways like heme biosynthesis and one-carbon metabolism [1,5,6]. Mutations in Slc25a38 are associated with congenital sideroblastic anemia (CSA), a disorder characterized by pathologic iron deposits in erythroblast mitochondria [1,3,4,5,7]. Mouse models have been valuable in studying its role.

Using CRISPR-CAS9 and conditional gene targeting, mouse models recapitulating SLC25A38-CSA have been developed. These models show an extreme hypersensitivity to pyridoxine deficiency, uncovering a conditional synthetic lethality between heme synthesis-related CSAs and pyridoxine deficiency [3]. Also, loss-of-function of Slc25a38 in erythroleukemia cells causes depletion of mitochondrial (but not cellular) pyridoxal 5'-phosphate, impairing cellular proliferation [2].

In conclusion, Slc25a38 is essential for mitochondrial pyridoxal 5'-phosphate accumulation and normal heme biosynthesis. The mouse models of SLC25A38-CSA have provided insights into the pathophysiology of congenital sideroblastic anemia and the conditional synthetic lethality with pyridoxine deficiency, potentially informing novel therapeutic strategies for this disease [2,3].