Background/purpose: LMBD1 protein, a type IV-B plasma membrane protein possessing nine putative trans-membrane domains, was previously demonstrated at cellular level to play a critical part in the signaling cascade of insulin receptor through its involvement in regulating clathrin-mediated endocytosis. However, at physiological level, the significance of LMBD1 protein in cardiac development remains unclear.
Methods: To understand the role of Lmbrd1 gene involved in the cardiac function, heterozygous knockout mice were used as an animal model system. The pathological outcomes were analyzed by micro-positron emission tomography, ECG acquisition, cardiac ultrasound, and immunohistochemistry.
Results: By studying the heterozygous knockout of Lmbrd1 (Lmbrd1+/-), we discovered that lack of Lmbrd1 not only resulted in the increase of cardiac-glucose uptake, pathological consequences were also observed. Here, we have distinguished that Lmbrd1+/- is sufficient in causing cardiac diseases through a pathway independent of the recessive vitamin B12 cblF cobalamin transport defect. Lmbrd1+/- mice exhibited an increase in myocardial glucose uptake and insulin receptor signaling that is insensitive to the administration of additional insulin. Pathological symptoms such as cardiac hypertrophy, ventricular tissue fibrosis, along with the increase of heart rate and cardiac muscle contractility were observed. As Lmbrd1+/- mice aged, the decrease in ejection fraction and fraction shortening showed signs of ventricular function deterioration.
Conclusion: The results suggested that Lmbrd1 gene not only plays a significant role in mediating the energy homeostasis in cardiac tissue, it may also be a key factor in the regulation of cardiac function in mice.
Keywords: Cardiac hypertrophy; Disease animal model; Gene knockout; Human LMBRD1 gene; LMBD1 protein; Mouse Lmbrd1 gene.
Copyright © 2017. Published by Elsevier B.V.