@inbook{11cd47e50438401b87051e2f18d39da2,
title = "Generating Ins2+/−/miR-133aTg Mice to Model miRNA-Driven Cardioprotection of Human Diabetic Heart",
abstract = "Diabetes mellitus (DM) is caused either due to insulin deficiency (T1DM) or insulin resistance (T2DM). DM increases the risk of heart failure by diabetic cardiomyopathy (DMCM), a cardiac muscle disorder that leads to a progressive decline in diastolic function, and ultimately systolic dysfunction. Mouse models of T1DM and T2DM exhibit clinical signs of DMCM. Growing evidence implicates microRNA (miRNA), an endogenous, non-coding, regulatory RNA, in the pathogenesis and signaling of DMCM. Therefore, inhibiting deleterious miRNAs and mimicking cardioprotective miRNAs could provide a potential therapeutic intervention for DMCM. miRNA-133a (miR-133a) is a highly abundant miRNA in the human heart. It is a cardioprotective miRNA, which is downregulated in the DM heart. It has anti-hypertrophic and anti-fibrotic effects. miR-133a mimic treatment after the onset of early DMCM can reverse histological and clinical signs of the disease in mice. We hypothesized that overexpression of cardiac-specific miR-133a in Ins2+/− Akita (T1DM) mice can prevent progression of DMCM. Here, we describe a method to create and validate cardiac-specific Ins2+/−/miR-133aTg mice to determine whether cardiac-specific miR-133a overexpression prevents development of DMCM. These strategies demonstrate the value of genetic modeling of human disease such as DMCM and evaluate the potential of miRNA as a therapeutic intervention.",
keywords = "Akita, Cardiac physiology, Diabetes models, Tissue-specific transgenic mice",
author = "Shahshahan, {Hamid R.} and Kambis, {Tyler N.} and Sumit Kar and Yadav, {Santosh K.} and Mishra, {Paras K.}",
note = "Funding Information: This study was supported, in part, by the National Institutes of Health grants HL-113281 and HL-116205 to Paras K. Mishra. We greatly appreciate Dr. Scot Matkovich from the Washington University, St. Louis for his kind gift of cardiac-specific miR-133aTg mice. Publisher Copyright: {\textcopyright} 2020, Springer Science+Business Media, LLC, part of Springer Nature.",
year = "2021",
doi = "10.1007/978-1-0716-1008-4_8",
language = "English (US)",
series = "Methods in Molecular Biology",
publisher = "Humana Press Inc.",
pages = "113--121",
booktitle = "Methods in Molecular Biology",
}