Single allele Lmbrd1 knockout results in cardiac hypertrophy
Journal
Journal of the Formosan Medical Association
Journal Volume
117
Journal Issue
6
Pages
471-479
Date Issued
2018
Author(s)
Tseng L.T.-L.
Lin C.-L.
Pan K.-H.
KAI-YUAN TZEN
Li Y.-H.
Abstract
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. ? 2017
SDGs
Other Subjects
alpha smooth muscle actin; cyanocobalamin; fluorodeoxyglucose f 18; glucose; insulin; insulin receptor; lactate dehydrogenase; lmbd1 protein; lmbrd1 protein; membrane protein; myosin heavy chain; unclassified drug; wortmannin; insulin receptor; Lmbrd1 protein, mouse; nucleocytoplasmic transport protein; aged; allele; animal experiment; animal model; animal tissue; Article; cyanocobalamin deficiency; deterioration; echocardiography; electrocardiogram; gene knockout; glucose transport; heart function; heart muscle contractility; heart rate; heart tissue; heart ventricle function; heart ventricle hypertrophy; heterozygote; immunohistochemistry; insulin blood level; insulin tolerance test; male; micro positron emission tomography; mouse; nonhuman; positron emission tomography; signal transduction; systolic dysfunction; allele; animal; cardiac muscle cell; cardiomegaly; diagnostic imaging; disease model; genetics; knockout mouse; metabolism; Alleles; Animals; Cardiomegaly; Disease Models, Animal; Echocardiography; Male; Mice; Mice, Knockout; Myocytes, Cardiac; Nucleocytoplasmic Transport Proteins; Positron-Emission Tomography; Receptor, Insulin; Signal Transduction
Publisher
Elsevier B.V.
Type
journal article