Normal mouse hearts (WT) and hearts with a mutation causing Dilated Cardiomyopathy showing the effect of the mutation on heart structure.

Dilated cardiomyopathy (DCM) is a serious, and poorly understood, heart disease that affects about 1 million people in the United State. DCM is a progressive disease with no current cure, often culminating in heart transplantation. Many cases of DCM are caused by inherited gene mutations often located on specific muscle proteins that are part of the cell machinery that allows contractions. One such protein is Myosin Light Chain 2 (MYL2), part of the “motor” that powers contraction. The investigators identified a human mutation that causes DCM called D94A, and created a transgenic mouse that expresses this mutation allowing the mouse heart muscle to be studied by a wide range of techniques including X-ray diffraction at the BioCAT Beamline 18ID at the Advanced Photon Source, Argonne National Laboratory. The X-ray experiments showed that one of the reasons the muscle does not contract correctly is that the myosin ”motor” proteins are positioned further away from their targets than in normal heart muscle making it harder for them to generate the correct amounts of force to pump the right amount of blood into circulation when the muscle contracts. These malfunctioning myosin motors perturb the structure of the sarcomere, the basic structural building block of muscle leading to changes in the gross structure of the D94A hearts resulting in the eventual development of DCM, much in the same way as in human patients. These results suggests that in addition to other sarcomeric genes, the MYL2 protein may be used as a target for new drugs designed to treat dilated cardiomyopathy disease.

See: Yuan CC, Kazmierczak K, Liang J, Zhou Z, Yadav S, Gomes AV, Irving TC, Szczesna-Cordary D. Sarcomeric perturbations of myosin motors lead to dilated cardiomyopathy in genetically modified MYL2 mice. Proc Natl Acad Sci USA. 2018 Mar 6;115(10):E2338-E2347. doi: 10.1073/pnas.1716925115. Epub 2018 Feb 20.