54,910 results match your criteria transgenic models


An in vivo Caenorhabditis elegans model for therapeutic research in human prion diseases.

Brain 2021 Oct;144(9):2745-2758

Paris Brain Institute, Inserm U 1127, CNRS UMR 7225, Sorbonne University, Hospital Pitié-Salpêtrière, F-75013 Paris, France.

Human prion diseases are fatal neurodegenerative disorders that include sporadic, infectious and genetic forms. Inherited Creutzfeldt-Jakob disease due to the E200K mutation of the prion protein-coding gene is the most common form of genetic prion disease. The phenotype resembles that of sporadic Creutzfeldt-Jakob disease at both the clinical and pathological levels, with a median disease duration of 4 months. Read More

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October 2021

Mitochondrial complex II in intestinal epithelial cells regulates T cell-mediated immunopathology.

Nat Immunol 2021 Oct 22. Epub 2021 Oct 22.

Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Rogel Cancer Center, Ann Arbor, MI, USA.

Intestinal epithelial cell (IEC) damage by T cells contributes to graft-versus-host disease, inflammatory bowel disease and immune checkpoint blockade-mediated colitis. But little is known about the target cell-intrinsic features that affect disease severity. Here we identified disruption of oxidative phosphorylation and an increase in succinate levels in the IECs from several distinct in vivo models of T cell-mediated colitis. Read More

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October 2021

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Drug Metab Dispos 2021 Oct 22. Epub 2021 Oct 22.

Environmental & Occupational Health Sciences, Univ Washington, United States.

Bile acids have been known for decades to aid in the digestion and absorption of dietary fats and fat-soluble vitamins in the intestine. The development of gene knockout mice models and transgenic humanized mouse models have helped us understand other function of bile acids, such as their role in modulating fat, glucose, and energy metabolism, and in the molecular regulation of the synthesis, transport, and homeostasis of bile acids. The G-protein coupled receptor TGR5 regulates the bile acid induced alterations of intermediary metabolism, while the nuclear receptor FXR regulates bile acid synthesis and homeostasis. Read More

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October 2021

Ion Channel Impairment and Myofilament Ca Sensitization: Two Parallel Mechanisms Underlying Arrhythmogenesis in Hypertrophic Cardiomyopathy.

Cells 2021 Oct 18;10(10). Epub 2021 Oct 18.

Division of Pharmacology, Department of Neuroscience, Psychology, Drug Sciences and Child Health (NeuroFarBa), University of Florence, 50139 Firenze, Italy.

Life-threatening ventricular arrhythmias are the main clinical burden in patients with hypertrophic cardiomyopathy (HCM), and frequently occur in young patients with mild structural disease. While massive hypertrophy, fibrosis and microvascular ischemia are the main mechanisms underlying sustained reentry-based ventricular arrhythmias in advanced HCM, cardiomyocyte-based functional arrhythmogenic mechanisms are likely prevalent at earlier stages of the disease. In this review, we will describe studies conducted in human surgical samples from HCM patients, transgenic animal models and human cultured cell lines derived from induced pluripotent stem cells. Read More

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October 2021

Coactivation of GSK3β and IGF-1 Attenuates Amyotrophic Lateral Sclerosis Nerve Fiber Cytopathies in SOD1 Mutant Patient-Derived Motor Neurons.

Cells 2021 Oct 16;10(10). Epub 2021 Oct 16.

Bioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 97002, Taiwan.

Amyotrophic lateral sclerosis (ALS) is a progressive nervous system disease that causes motor neuron (MN) degeneration and results in patient death within a few years. To recapitulate the cytopathies of ALS patients' MNs, mutant and corrected isogenic-induced pluripotent stem cell (iPSC) lines were established. Two mutant ALS ( and ), two mutant corrected ( and ), and one sporadic ALS iPSC lines were directed toward MNs. Read More

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October 2021

A Novel Calpain Inhibitor Compound Has Protective Effects on a Zebrafish Model of Spinocerebellar Ataxia Type 3.

Cells 2021 Sep 29;10(10). Epub 2021 Sep 29.

Neurodegeneration Treatment Team, Centre for Motor Neuron Disease Research, Faculty of Medicine, Health and Human Sciences, Macquarie Medical School, Macquarie University, Sydney 2109, Australia.

Spinocerebellar ataxia type 3 (SCA3) is a hereditary ataxia caused by inheritance of a mutated form of the human gene containing an expanded CAG repeat region, encoding a human ataxin-3 protein with a long polyglutamine (polyQ) repeat region. Previous studies have demonstrated that ataxin-3 containing a long polyQ length is highly aggregation prone. Cleavage of the ataxin-3 protein by calpain proteases has been demonstrated to be enhanced in SCA3 models, leading to an increase in the aggregation propensity of the protein. Read More

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September 2021

A Tendon-Specific Double Reporter Transgenic Mouse Enables Tracking Cell Lineage and Functions Alteration In Vitro and In Vivo.

Int J Mol Sci 2021 Oct 17;22(20). Epub 2021 Oct 17.

Department of Neuroanatomy, Group for Regeneration and Reprogramming, Institute for Anatomy and Cell Biology, Medical Faculty, Heidelberg University, 69120 Heidelberg, Germany.

We generated and characterized a transgenic mouse line with the tendon-specific expression of a double fluorescent reporter system, which will fulfill an unmet need for animal models to support real-time monitoring cell behaviors during tendon development, growth, and repair in vitro and in vivo. The mScarlet red fluorescent protein is driven by the () promoter to report the cell lineage alteration. The blue fluorescent protein reporter is expressed under the control of the 3. Read More

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October 2021

The Expression and Localisation of G-Protein-Coupled Inwardly Rectifying Potassium (GIRK) Channels Is Differentially Altered in the Hippocampus of Two Mouse Models of Alzheimer's Disease.

Int J Mol Sci 2021 Oct 14;22(20). Epub 2021 Oct 14.

Synaptic Structure Laboratory, Instituto de Investigación en Discapacidades Neurológicas (IDINE), Departamento de Ciencias Médicas, Facultad de Medicina, Universidad Castilla-La Mancha, Campus Biosanitario, C/Almansa 14, 02008 Albacete, Spain.

G protein-gated inwardly rectifying K (GIRK) channels are the main targets controlling excitability and synaptic plasticity on hippocampal neurons. Consequently, dysfunction of GIRK-mediated signalling has been implicated in the pathophysiology of Alzheimer´s disease (AD). Here, we provide a quantitative description on the expression and localisation patterns of GIRK2 in two transgenic mice models of AD (P301S and APP/PS1 mice), combining histoblots and immunoelectron microscopic approaches. Read More

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October 2021

Esculetin Provides Neuroprotection against Mutant Huntingtin-Induced Toxicity in Huntington's Disease Models.

Pharmaceuticals (Basel) 2021 Oct 13;14(10). Epub 2021 Oct 13.

Department for Life Quality Studies, University of Bologna, 47921 Rimini, Italy.

Huntington's disease (HD) is a neurodegenerative disorder caused by an abnormal CAG trinucleotide repeat expansion within exon 1 of the huntingtin (HTT) gene. This mutation leads to the production of mutant HTT (mHTT) protein which triggers neuronal death through several mechanisms. Here, we investigated the neuroprotective effects of esculetin (ESC), a bioactive phenolic compound, in an inducible PC12 model and a transgenic model of HD, both of which express mHTT fragments. Read More

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October 2021

Inducible Liver Cancer Models in Transgenic Zebrafish to Investigate Cancer Biology.

Cancers (Basel) 2021 Oct 14;13(20). Epub 2021 Oct 14.

Department of Biological Sciences, National University of Singapore, Singapore 119077, Singapore.

Primary liver cancer is one of the most prevalent and deadly cancers, which incidence continues to increase while treatment response remains poor; thus, in-depth understanding of tumour events is necessary to develop more effective therapies. Animal models for liver cancer are powerful tools to reach this goal. Over the past decade, our laboratory has established multiple oncogene transgenic zebrafish lines that can be robustly induced to develop liver cancer. Read More

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October 2021

Protective Effects of Lignin-Carbohydrate Complexes from Wheat Stalk against Bisphenol a Neurotoxicity in Zebrafish via Oxidative Stress.

Antioxidants (Basel) 2021 Oct 18;10(10). Epub 2021 Oct 18.

Nanjing Institute of Environmental Sciences, Ministry of Ecology and Environment, Jiangwangmiao Street 8, Nanjing 210042, China.

Lignin-carbohydrate complexes (LCCs) from different lignocellulosic biomass have shown biological qualities as antioxidant and immunostimulant. By contrast, the application of LCCs as protectant against neurotoxicity caused by different compounds is scarce. In this work, two kinds of LCCs with carbohydrate-rich and lignin-rich fractions were obtained from wheat stalk and used to protect against BPA-neurotoxicity in zebrafish. Read More

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October 2021

Pathogenic tau accelerates aging-associated activation of transposable elements in the mouse central nervous system.

Prog Neurobiol 2021 Oct 17:102181. Epub 2021 Oct 17.

Barshop Institute for Longevity and Aging Studies, United States; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, United States; Department of Cell Systems and Anatomy, University of Texas Health San Antonio, San Antonio, Texas, United States. Electronic address:

Transposable elements comprise almost half of the mammalian genome. A growing body of evidence suggests that transposable element dysregulation accompanies brain aging and neurodegenerative disorders, and that transposable element activation is neurotoxic. Recent studies have identified links between pathogenic forms of tau, a protein that accumulates in Alzheimer's disease and related "tauopathies," and transposable element-induced neurotoxicity. Read More

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October 2021

SARS-CoV-2 causes lung infection without severe disease in human ACE2 knock-in mice.

J Virol 2021 Oct 20:JVI0151121. Epub 2021 Oct 20.

Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.

The development of mouse models for COVID-19 has enabled testing of vaccines and therapeutics and defining aspects of SARS-CoV-2 pathogenesis. SARS-CoV-2 disease is severe in K18 transgenic mice (K18-hACE2-Tg) expressing human ACE2 (hACE2), the SARS-CoV-2 receptor, under an ectopic cytokeratin promoter, with high levels of infection measured in the lung and brain. Here, we evaluated SARS-CoV-2 infection in hACE2 KI mice that express hACE2 under an endogenous promoter in place of murine ACE2 (mACE2). Read More

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October 2021

The K18-hACE2 Transgenic Mouse Model Recapitulates Non-Severe and Severe COVID-19 in Response to Infectious Dose of SARS-CoV-2 Virus.

J Virol 2021 Oct 20:JVI0096421. Epub 2021 Oct 20.

Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California, USA.

A comprehensive analysis and characterization of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection model that mimics non-severe and severe coronavirus disease 2019 (COVID-19) in humans is warranted for understating the virus and developing preventive and therapeutic agents. Here, we characterized the K18-hACE2 mouse model expressing human (h)ACE2 in mice, controlled by the human keratin 18 (K18) promoter, in the epithelia, including airway epithelial cells where SARS-CoV-2 infections typically start. We found that intranasal inoculation with higher viral doses (2×10 and 2×10 PFU) of SARS-CoV-2 caused lethality of all mice and severe damage of various organs, including lung, liver, and kidney, while lower doses (2×10 and 2×10 PFU) led to less severe tissue damage and some mice recovered from the infection. Read More

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October 2021

Color-Coded Imaging of the Tumor Microenvironment (TME) in Human Patient-Derived Orthotopic Xenograft (PDOX) Mouse Models.

Adv Exp Med Biol 2021 ;1329:163-179

AntiCancer, Inc., San Diego, CA, USA.

The tumor microenvironment (TME) contains stromal cells in a complex interaction with cancer cells. This relationship has become better understood with the use of fluorescent proteins for in vivo imaging, originally developed by our laboratories. Spectrally distinct fluorescent proteins can be used for color-coded imaging of the complex interaction of the tumor microenvironment in the living state using cancer cells expressing a fluorescent protein of one color and host mice expressing another color fluorescent protein. Read More

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October 2021

Measuring Amyloid-β Peptide Concentrations in Murine Brain with Improved ELISA Assay.

Curr Protoc 2021 Oct;1(10):e253

Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.

The amyloid-β (Aβ) peptides of 40 and 42 amino acids that are implicated in Alzheimer's disease may potentially aggregate into toxic oligomers and form neuritic plaques. The enzyme-linked immunosorbent assay (ELISA) is a facile method used for the determination of Aβ concentrations in biological matrices, namely plasma, cerebrospinal fluid, and brain. The method is mostly used for the measurement of Aβ concentrations in transgenic mice, but it is unknown whether the ELISA method is suitable for measuring low, endogenous levels of Aβ in the brains of wild-type mice. Read More

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October 2021

Measurement of Glutamate Uptake using Radiolabeled L-[3H]-Glutamate in Acute Transverse Slices Obtained from Rodent Resected Hippocampus.

J Vis Exp 2021 10 2(176). Epub 2021 Oct 2.

Department of Biological Sciences, Universidade Federal de Ouro Preto; Programa de Pós-Graduação em Ciências Biológicas, Universidade Federal de Ouro Preto;

Glutamate removal from the extracellular space by high-affinity Na-dependent transporters is essential to ensure that the brain's intrinsic connectivity mechanisms work properly and homeostasis is maintained. The hippocampus is a unique brain structure that manages higher cognitive functions, and is the subject of several studies regarding neurologic diseases. The investigation of physiological and pathological mechanisms in rodent models can benefit from acute hippocampal slice (AHS) preparations. Read More

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October 2021

4-Hydroxy-2-Nonenal Promotes Cardiomyocyte Necroptosis Stabilizing Receptor-Interacting Serine/Threonine-Protein Kinase 1.

Front Cell Dev Biol 2021 1;9:721795. Epub 2021 Oct 1.

Department of Emergency and Chest Pain Center, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Necroptosis is a vital regulator of myocardial ischemia/reperfusion (MI/R) injury. Meanwhile, 4-hydroxy-2-nonenal (4-HNE) is abundantly increased during MI/R injury. However, whether 4-HNE induces cardiomyocyte necroptosis during MI/R remains unknown. Read More

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October 2021

Monocyte Chemotactic Protein-Induced Protein 1 (MCPIP-1): A Key Player of Host Defense and Immune Regulation.

Front Immunol 2021 1;12:727861. Epub 2021 Oct 1.

Office of Human Research, Memorial Healthcare System, Hollywood, FL, United States.

Inflammatory response is a host-protective mechanism against tissue injury or infections, but also has the potential to cause extensive immunopathology and tissue damage, as seen in many diseases, such as cardiovascular diseases, neurodegenerative diseases, metabolic syndrome and many other infectious diseases with public health concerns, such as Coronavirus Disease 2019 (COVID-19), if failure to resolve in a timely manner. Recent studies have uncovered a superfamily of endogenous chemical molecules that tend to resolve inflammatory responses and re-establish homeostasis without causing excessive damage to healthy cells and tissues. Among these, the monocyte chemoattractant protein-induced protein (MCPIP) family consisting of four members (MCPIP-1, -2, -3, and -4) has emerged as a group of evolutionarily conserved molecules participating in the resolution of inflammation. Read More

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October 2021

Positive and Negative Selective Allosteric Modulators of α5 GABAA Receptors: Effects on Emotionality, Motivation, and Motor Function in the 5xFAD Model of Alzheimer's Disease.

J Alzheimers Dis 2021 Oct 10. Epub 2021 Oct 10.

Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.

Background: Positive and negative allosteric modulators of α5 GABAA receptors (PAM and NAM, respectively) are worthy of investigation as putative treatments of Alzheimer's disease (AD). However, their potential to modify a dynamic range of behaviors in AD models needs to be systematically examined.

Objective: The study aimed to assess effects of MP-III-022 as PAM and PWZ-029 as NAM on emotional reactivity, motivation, and motor function, as well as on gene expression of GABRA2, GABRA3 and GABRA5 subunit of GABAA receptors in prefrontal cortex (PFC) and hippocampus (HC) in 5xFAD mice, as an early-onset transgenic AD model. Read More

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October 2021

A HER2 target antibody drug conjugate combined with anti-PD-(L)1 treatment eliminates hHER2+ tumors in hPD-1 transgenic mouse model and contributes immune memory formation.

Breast Cancer Res Treat 2021 Oct 16. Epub 2021 Oct 16.

Laboratory of Molecular Medicine, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, People's Republic of China.

Purpose: Disitamab vedotin (RC48) is an HER2-directed antibody-drug conjugate, emerging as an effective strategy for cancer therapy, which not only enhances antitumor immunity in previous animal models but also improves clinical outcomes for patients such as with gastric cancer, urothelium carcinoma, and HER2 low-expressing breast cancer. Here, we explore the combination therapeutic efficacy of this novel HER2-targeting ADC with immune checkpoint inhibitors in a human HER2-expressing syngeneic breast cancer model.

Methods: The human HER2+ cancer cell line is constructed by stable transfection and individual clones were isolated by single-cell sorting. Read More

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October 2021

Characterization of an APP/tau rat model of Alzheimer's disease by positron emission tomography and immunofluorescent labeling.

Alzheimers Res Ther 2021 Oct 16;13(1):175. Epub 2021 Oct 16.

Preclinical Molecular Imaging, AIT Austrian Institute of Technology GmbH, 2444, Seibersdorf, Austria.

Background: To better understand the etiology and pathomechanisms of Alzheimer's disease, several transgenic animal models that overexpress human tau or human amyloid-beta (Aβ) have been developed. In the present study, we generated a novel transgenic rat model by cross-breeding amyloid precursor protein (APP) rats with tau rats. We characterized this model by performing positron emission tomography scans combined with immunofluorescent labeling and cerebrospinal fluid analyses. Read More

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October 2021

Tau in the brain interstitial fluid is fragmented and seeding-competent.

Neurobiol Aging 2021 Sep 17;109:64-77. Epub 2021 Sep 17.

AbbVie Deutschland GmbH & Co. KG , Neuroscience Discovery, Knollstrasse, Ludwigshafen, Germany. Electronic address:

In Alzheimer disease, Tau pathology is thought to propagate from cell to cell throughout interconnected brain areas. However, the forms of Tau released into the brain interstitial fluid (ISF) in vivo during the development of Tauopathy and their pathological relevance remain unclear. Combining in vivo microdialysis and biochemical analysis, we find that in Tau transgenic mice, human Tau (hTau) present in brain ISF is truncated and comprises at least 10 distinct fragments spanning the entire Tau protein. Read More

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September 2021

Systematic phenotyping and characterization of the 5xFAD mouse model of Alzheimer's disease.

Sci Data 2021 Oct 15;8(1):270. Epub 2021 Oct 15.

Institute for Memory Impairments and Neurological Disorders (UCI MIND), University of California, Irvine, CA, 92697, USA.

Mouse models of human diseases are invaluable tools for studying pathogenic mechanisms and testing interventions and therapeutics. For disorders such as Alzheimer's disease in which numerous models are being generated, a challenging first step is to identify the most appropriate model and age to effectively evaluate new therapeutic approaches. Here we conducted a detailed phenotypic characterization of the 5xFAD model on a congenic C57BL/6 J strain background, across its lifespan - including a seldomly analyzed 18-month old time point to provide temporally correlated phenotyping of this model and a template for characterization of new models of LOAD as they are generated. Read More

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October 2021

Discovery of Potent, Selective, and Brain-Penetrant Apoptosis Signal-Regulating Kinase 1 (ASK1) Inhibitors that Modulate Brain Inflammation .

J Med Chem 2021 Oct 15. Epub 2021 Oct 15.

Medicinal Chemistry, Biogen, 225 Binney Street, Cambridge, Massachusetts 02142, United States.

Apoptosis signal-regulating kinase 1 (ASK1) is one of the key mediators of the cellular stress response that regulates inflammation and apoptosis. To probe the therapeutic value of modulating this pathway in preclinical models of neurological disease, we further optimized the profile of our previously reported inhibitor . This effort led to the discovery of , a potent (cell IC = 25 nM) and selective ASK1 inhibitor with suitable pharmacokinetic and brain penetration (rat Cl/Cl = 1. Read More

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October 2021

Generation of an Lpar1-EGFP Fusion Knock-in Transgenic Mouse Line.

Cell Biochem Biophys 2021 Oct 15. Epub 2021 Oct 15.

Translational Neuroscience Initiative, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.

Lysophosphatidic acid (LPA) is a lysophospholipid that acts as an extracellular signal through the activation of cognate G protein-coupled receptors (GPCRs). There are six known LPA receptors (LPA). The first such receptor, LPA, was identified in the embryonic brain and has been studied extensively for gene expression throughout the body, including through studies of receptor-null mice. Read More

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October 2021

Histological Findings of Mammary Gland Development and Risk of Breast Cancer in Mutant Mouse Models.

J Breast Cancer 2021 Oct 5. Epub 2021 Oct 5.

Department of Radiology, Seoul National University Hospital, Seoul, Korea.

Purpose: The breast cancer susceptibility gene, , is involved in normal development and carcinogenesis of mammary glands. Here, we aimed to evaluate the relationship between histological findings of mammary gland development and breast cancer risk in mutant mice.

Methods: Five mutant mice and five non-mutant FVB/NJ mice were used for each group of 1-month-old (pubertal), 3-month-old (fertile), and 8-month-old (menopausal) mice. Read More

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October 2021

Diallyl sulfide protects against dilated cardiomyopathy via inhibition of oxidative stress and apoptosis in mice.

Mol Med Rep 2021 Dec 15;24(6). Epub 2021 Oct 15.

Key Laboratory of Human Disease Comparative Medicine, National Health Commission of China (NHC), Institute of Laboratory Animal Science, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100021, P.R. China.

Cytochrome P450 family 2 subfamily E member 1 (CYP2E1) is a member of the cytochrome P450 enzyme family and catalyzes the metabolism of various substrates. CYP2E1 is upregulated in multiple heart diseases and causes damage mainly via the production of reactive oxygen species (ROS). In mice, increased CYP2E1 expression induces cardiac myocyte apoptosis, and knockdown of endogenous CYP2E1 can attenuate the pathological development of dilated cardiomyopathy (DCM). Read More

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December 2021

Genetic inhibition of Nuclear Factor of Activated T-cell c2 (NFATc2) prevents atrial fibrillation in CREM transgenic mice.

Cardiovasc Res 2021 Oct 14. Epub 2021 Oct 14.

Cardiovascular Research Institute.

Aims: Abnormal intracellular calcium handling contributes to the progressive nature of atrial fibrillation (AF), the most common sustained cardiac arrhythmia. Evidence in mouse models suggests that activation of the nuclear factor of activated T-cell (NFAT) signaling pathway contributes to atrial remodeling. Our aim was to determine the role of NFATc2 in AF in humans and mouse models. Read More

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October 2021