36,598 results match your criteria studies transgenic

Development of a Novel Human CD147 Transgenic NSG Mouse Model to test SARS-CoV-2 Infection and Immune Responses.

Res Sq 2021 Apr 7. Epub 2021 Apr 7.

An animal model that can mimic the SARS-CoV-2 infection in humans is critical to understanding the newly emerged, rapidly spreading SARS-CoV-2 and development of therapeutic strategies. Studies show that the spike (S) proteins of SARS-CoV (SARS-CoV-S-1-S) and SARS-CoV-2 (SARS-CoV-2-S) bind to human angiotensin-converting enzyme 2 (hACE2, a well-recognized, functional receptor for SARS-CoV and SARS-CoV-2) to mediate viral entry. Several hACE2 transgenic (hACE2Tg) mouse models are being widely used, which is clearly invaluable. Read More

View Article and Full-Text PDF

Novel reporter mouse models useful for evaluating gene editing and for optimization of methods of delivering genome editing tools.

Mol Ther Nucleic Acids 2021 Jun 5;24:325-336. Epub 2021 Mar 5.

Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Kanagawa, Japan.

The clustered regularly interspersed palindromic repeats (CRISPR) system is a powerful genome-editing tool to modify genomes, virtually in any species. The CRISPR tool has now been utilized in many areas of medical research, including gene therapy. Although several proof-of-concept studies show the feasibility of gene therapy applications for correcting disease-causing mutations, and new and improved tools are constantly being developed, there are not many choices of suitable reporter models to evaluate genome editor tools and their delivery methods. Read More

View Article and Full-Text PDF

affects oxidative stress and pyroptosis in hippocampal neurons of Alzheimer's disease mouse model by regulating the Nrf2 pathway.

Lin Cheng Wei Zhang

Exp Ther Med 2021 Jun 26;21(6):557. Epub 2021 Mar 26.

Zhang Zhongjing College of Chinese Medicine, Nanyang Institute of Technology, Nanyang, Henan 473004, P.R. China.

Studies have confirmed that is associated with diseases associated with the nervous system, including Alzheimer's disease (AD). However, the role of in the pathogenesis of AD has not been clarified. To investigate the effect of on brain tissue damage and cognitive function in AD mice and its possible mechanism, 5XFAD transgenic mice were used as AD model mice and in the brain was overexpressed by transfection of a lentiviral containing a specific targeting gene into the bilateral hippocampus of mice. Read More

View Article and Full-Text PDF

Adiponectin-mimetic novel nonapeptide rescues aberrant neuronal metabolic-associated memory deficits in Alzheimer's disease.

Mol Neurodegener 2021 Apr 13;16(1):23. Epub 2021 Apr 13.

Division of Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, Jinju, 52828, Republic of Korea.

Background: Recently, we and other researchers reported that brain metabolic disorders are implicated in Alzheimer's disease (AD), a progressive, devastating and incurable neurodegenerative disease. Hence, novel therapeutic approaches are urgently needed to explore potential and novel therapeutic targets/agents for the treatment of AD. The neuronal adiponectin receptor 1 (AdipoR1) is an emerging potential target for intervention in metabolic-associated AD. Read More

View Article and Full-Text PDF

Abnormal patterns of sleep and EEG power distribution during non-rapid eye movement sleep in the sheep model of Huntington's disease.

Neurobiol Dis 2021 Apr 10:105367. Epub 2021 Apr 10.

Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3DY, United Kingdom. Electronic address:

Sleep disruption is a common invisible symptom of neurological dysfunction in Huntington's disease (HD) that takes an insidious toll on well-being of patients. Here we used electroencephalography (EEG) to examine sleep in 6 year old OVT73 transgenic sheep (Ovis aries) that we used as a presymptomatic model of HD. We hypothesized that despite the lack of overt symptoms of HD at this age, early alterations of the sleep-wake pattern and EEG powers may already be present. Read More

View Article and Full-Text PDF

Passive immunotherapy with a novel antibody against 3pE-modified Aβ demonstrates potential for enhanced efficacy and favorable safety in combination with BACE inhibitor treatment in plaque-depositing mice.

Neurobiol Dis 2021 Apr 10:105365. Epub 2021 Apr 10.

Department of Neuroscience, Janssen Research & Development, A division of Janssen Pharmaceutica NV, Beerse, Belgium. Electronic address:

The imbalance between production and clearance of amyloid β (Aβ) peptides and their resulting accumulation in the brain is an early and crucial step in the pathogenesis of Alzheimer's disease (AD). Therefore, Aβ is strongly positioned as a promising and extensively validated therapeutic target for AD. Investigational disease-modifying approaches aiming at reducing cerebral Aβ concentrations include prevention of de novo production of Aβ through inhibition of β-site amyloid precursor protein cleaving enzyme 1 (BACE1), and clearance of Aβ deposits via passive Aβ immunotherapy. Read More

View Article and Full-Text PDF

Generation of a tissue-specific transgenic model for K8 phosphomutants: A tool to investigate the role of K8 phosphorylation during skin carcinogenesis in vivo.

Cell Biol Int 2021 Apr 13. Epub 2021 Apr 13.

Advanced Centre for Treatment, Research, and Education in Cancer, Navi Mumbai, 410210, India.

Keratin 8/18, the predominant keratin pair of simple epithelia, is known to be aberrantly expressed in several squamous cell carcinomas, where its expression is often correlated with increased invasion, neoplastic progression, and poor prognosis. The majority of keratin 8/18 structural and regulatory functions are governed by post-translational modifications, particularly phosphorylation. Apart from filament reorganization, cellular processes including cell cycle, cell growth, cellular stress, and apoptosis are known to be orchestrated by K8 phosphorylation at specific residues in the head and tail domains. Read More

View Article and Full-Text PDF

Temporal contribution of myeloid-lineage TLR4 to the transition to chronic pain: A focus on sex differences.

J Neurosci 2021 Apr 10. Epub 2021 Apr 10.

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, CA 94305, USA

Complex regional pain syndrome (CRPS) is a chronic pain disorder with a clear acute-to-chronic transition. Preclinical studies demonstrate that toll-like receptor 4 (TLR4), expressed by myeloid-lineage cells, astrocytes, and neurons, mediates a sex-dependent transition to chronic pain; however, evidence is lacking on which exact TLR4-expressing cells are responsible. We used complementary pharmacologic and transgenic approaches in mice to more specifically manipulate myeloid-lineage TLR4 and outline its contribution to the transition from acute-to-chronic CRPS based on three key variables: location (peripheral vs. Read More

View Article and Full-Text PDF

Modulation of Huntington's disease in Drosophila.

CNS Neurol Disord Drug Targets 2021 Apr 12. Epub 2021 Apr 12.

Drosophila Transgenic Laboratory, Section of Genetics, Department of Zoology, Faculty of Life Sciences, Aligarh Muslim University, Aligarh-202002, Uttar Pradesh. India.

Huntington's disease (HD) is a progressive neurodegenerative disorder which deteriorates the physical and mental abilities of the patients. It is an autosomal dominant disorder and is mainly caused by the expansion of a repeating CAG triplet. A number of animal models ranging from worms, fruit flies, mice and rats to pigs, sheep and monkeys are available which have been helpful in understanding various pathways involved during the progression of the disease. Read More

View Article and Full-Text PDF

Chemogenetic manipulation of astrocytic signaling in the basolateral amygdala reduces binge-like alcohol consumption in male mice.

J Neurosci Res 2021 Apr 12. Epub 2021 Apr 12.

Department of Biological & Biomedical Sciences, North Carolina Central University, Durham, NC, USA.

Binge drinking is a common occurrence in the United States, but a high concentration of alcohol in the blood has been shown to have reinforcing and reciprocal effects on the neuroimmune system in both dependent and non-dependent scenarios. The first part of this study examined alcohol's effects on the astrocytic response in the central amygdala and basolateral amygdala (BLA) in a non-dependent model. C57BL/6J mice were given access to either ethanol, water, or sucrose during a "drinking in the dark" paradigm, and astrocyte number and astrogliosis were measured using immunohistochemistry. Read More

View Article and Full-Text PDF

Neuronal Hyperexcitability in APPSWE/PS1dE9 Mouse Models of Alzheimer's Disease.

J Alzheimers Dis 2021 Apr 5. Epub 2021 Apr 5.

Department of Psychosomatic Medicine and Psychotherapy, University of Rostock, Rostock, Germany.

Transgenic mouse models serve a better understanding of Alzheimer's disease (AD) pathogenesis and its consequences on neuronal function. Well-known and broadly used AD models are APPswe/PS1dE9 mice, which are able to reproduce features of amyloid-β (Aβ) plaque formations as well as neuronal dysfunction as reflected in electrophysiological recordings of neuronal hyperexcitability. The most prominent findings include abnormal synaptic function and synaptic reorganization as well as changes in membrane threshold and spontaneous neuronal firing activities leading to generalized excitation-inhibition imbalances in larger neuronal circuits and networks. Read More

View Article and Full-Text PDF

Epigenetic regulation in Alzheimer's disease: is it a potential therapeutic target?

Fabio Coppedè

Expert Opin Ther Targets 2021 Apr 12. Epub 2021 Apr 12.

Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, Via Roma 55, 56126 Pisa, Italy.

Introduction: Alzheimer's disease (AD) is the most common neurodegenerative disorder and the primary form of dementia in the elderly. Changes in DNA methylation and post-translational modifications of histone tails are increasingly observed in AD tissues, and likely contribute to disease onset and progression. The reversibility of these epigenetic marks offers the potential for therapeutic interventions. Read More

View Article and Full-Text PDF

Effects of long-acting analogues of lamprey GLP-1 and paddlefish glucagon on alpha- to beta-cell transdifferentiation in an insulin-deficient transgenic mouse model.

J Pept Sci 2021 Apr 11:e3328. Epub 2021 Apr 11.

Diabetes Research Group, School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine, BT52 1SA, UK.

The abilities of the long-acting, dual-agonist anti-diabetic peptides [D-Ala ]palmitoyl-lamprey GLP-1 and [D-Ser ]palmitoyl-paddlefish glucagon to induce α-cell to β-cell transdifferentiation were investigated in Glu ;ROSA26-eYFP mice. These animals have been genetically engineered so that yellow fluorescent protein is specifically expressed in glucagon-producing α-cells, thereby allowing cell lineage tracing. Insulin deficiency was produced by treatment of the mice with multiple low doses of streptozotocin. Read More

View Article and Full-Text PDF

Aging-associated skeletal muscle defects in HER2/Neu transgenic mammary tumor model.

JCSM Rapid Commun 2021 Jan-Jun;4(1):24-39. Epub 2020 Jul 15.

Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

Background: Loss of skeletal muscle volume and resulting in functional limitations are poor prognostic markers in breast cancer patients. Several molecular defects in skeletal muscle including reduced MyoD levels and increased protein turn over due to enhanced proteosomal activity have been suggested as causes of skeletal muscle loss in cancer patients. However, it is unknown whether molecular defects in skeletal muscle are dependent on tumor etiology. Read More

View Article and Full-Text PDF

Ion Channels Orchestrate Pancreatic Ductal Adenocarcinoma Progression and Therapy.

Front Pharmacol 2020 19;11:586599. Epub 2021 Jan 19.

Institute of Physiology II, University of Münster, Münster, Germany.

Pancreatic ductal adenocarcinoma is a devastating disease with a dismal prognosis. Therapeutic interventions are largely ineffective. A better understanding of the pathophysiology is required. Read More

View Article and Full-Text PDF
January 2021

Characterization of nonmotor behavioral impairments and their neurochemical mechanisms in the MitoPark mouse model of progressive neurodegeneration in Parkinson's disease.

Exp Neurol 2021 Apr 8:113716. Epub 2021 Apr 8.

Parkinson Disorders Research Program, Iowa Center for Advanced Neurotoxicology, Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, United States of America.

Mitochondrial dysfunction has been implicated as a key player in the pathogenesis of Parkinson's disease (PD). The MitoPark mouse, a transgenic mitochondrial impairment model developed by specific inactivation of TFAM in dopaminergic neurons, spontaneously exhibits progressive motor deficits and neurodegeneration, recapitulating several features of PD. Since nonmotor symptoms are now recognized as important features of the prodromal stage of PD, we comprehensively assessed the clinically relevant motor and nonmotor deficiencies from ages 8-24 wk. Read More

View Article and Full-Text PDF

Photoreceptor ablation following ATP induced injury triggers Müller glia driven regeneration in zebrafish.

Exp Eye Res 2021 Apr 8:108569. Epub 2021 Apr 8.

Australian Regenerative Medicine Institute, Monash University, Clayton, VIC, 3800, Australia; School of BioSciences, University of Melbourne, Parkville, VIC, 3010, Australia. Electronic address:

Retinal regeneration research offers hope to people affected by visual impairment due to disease and injury. Ongoing research has explored many avenues towards retinal regeneration, including those that utilizes implantation of devices, cells or targeted viral-mediated gene therapy. These results have so far been limited, as gene therapy only has applications for rare single-gene mutations and implantations are invasive and in the case of cell transplantation donor cells often fail to integrate with adult neurons. Read More

View Article and Full-Text PDF

Pituitary tumors and immortalized cell lines generated by cre-inducible expression of SV40 T antigen.

Endocrinology 2021 Apr 10. Epub 2021 Apr 10.

University of Michigan Medical School, Ann Arbor, MI, USA.

Targeted oncogenesis is the process of driving tumor formation by engineering transgenic mice that express an oncogene under the control of a cell-type specific promoter. Such tumors can be adapted to cell culture, providing immortalized cell lines. To make it feasible to follow the process of tumorigenesis and increase the opportunity for generating cell lines, we developed a mouse strain that expresses SV40 T antigens in response to cre-recombinase. Read More

View Article and Full-Text PDF

Total number and ratio of GABAergic neuron types in the mouse lateral and basal amygdala.

J Neurosci 2021 Apr 6. Epub 2021 Apr 6.

ELRN Institute of Experimental Medicine, 1083 Budapest, Hungary

GABAergic neurons are key circuit elements in cortical networks. In spite of growing evidence showing that inhibitory cells play a critical role in the lateral (LA) and basal (BA) amygdala functions, neither the number of GABAergic neurons nor the ratio of their distinct types have been determined in these amygdalar nuclei. Using unbiased stereology, we found that the ratio of GABAergic neurons in the BA (22%) is significantly higher than in the LA (16%) in both male and female mice. Read More

View Article and Full-Text PDF

Animal Models of COVID-19. I. Comparative Virology and Disease Pathogenesis.

ILAR J 2021 Apr 9. Epub 2021 Apr 9.

Department of Comparative Medicine, John Hopkins School of Medicine, Baltimore, Maryland, USA.

The Coronavirus Disease 2019 (COVID-19) pandemic has fueled unprecedented development of animal models to understand disease pathogenesis, test therapeutics, and support vaccine development. Models previously developed to study severe acute respiratory syndrome coronavirus (SARS-CoV) have been rapidly deployed to study SARS-CoV-2. However, it has become clear that despite the common use of ACE2 as a receptor for both viruses, the host range of the 2 viruses does not entirely overlap. Read More

View Article and Full-Text PDF

Modeling the mature CNS: A predictive screening platform for neurodegenerative disease drug discovery.

J Neurosci Methods 2021 Apr 6:109180. Epub 2021 Apr 6.

Cognition Therapeutics Inc., Pittsburgh, PA, 15203, United States. Electronic address:

Background: Mature primary neuronal cultures are an important model of the nervous system, but limited scalability has been a major challenge in their use for drug discovery of neurodegenerative diseases. This work describes a method for improving scalability through the use of larger format microtiter plates while preserving culture quality.

New Method: Here we describe a method and quality control procedures for growing embryonic day 18 rat hippocampal/cortical neuronal cultures in 384-well microtiter plates for three weeks in vitro. Read More

View Article and Full-Text PDF

TOP1 inhibition therapy protects against SARS-CoV-2-induced lethal inflammation.

Cell 2021 Mar 30. Epub 2021 Mar 30.

Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address:

The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently affecting millions of lives worldwide. Large retrospective studies indicate that an elevated level of inflammatory cytokines and pro-inflammatory factors are associated with both increased disease severity and mortality. Here, using multidimensional epigenetic, transcriptional, in vitro, and in vivo analyses, we report that topoisomerase 1 (TOP1) inhibition suppresses lethal inflammation induced by SARS-CoV-2. Read More

View Article and Full-Text PDF

Adhesion Receptor Adgrg2/Gpr64 Is In The Gi-Tract Selectively Expressed In Mature Intestinal Tuft Cells.

Mol Metab 2021 Apr 5:101231. Epub 2021 Apr 5.

NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3, 2200, Copenhagen, Denmark. Electronic address:

Objective: GPR64/ADGRG2 is an orphan Adhesion G protein-coupled receptor (ADGR) known mainly to be expressed in parathyroid gland and epididymis. The aim of this investigation was to delineate the cellular expression of GPR64 throughout the body with focus on the GI tract.

Methods: Transgenic Gpr64 reporter mice were histologically examined throughout the body and reporter protein expression in intestinal tuft cells was confirmed by specific cell ablation. Read More

View Article and Full-Text PDF

Serotonin Transporter Ala276 Mouse: Novel Model to Assess the Neurochemical and Behavioral Impact of Thr276 Phosphorylation In Vivo.

Neurochem Res 2021 Apr 8. Epub 2021 Apr 8.

Department of Biomedical Science, Charles E. Schmidt College of Medicine, Florida Atlantic University, Jupiter, FL, USA.

The serotonin (5-HT) transporter (SERT) is a key regulator of 5-HT signaling and is a major target for antidepressants and psychostimulants. Human SERT coding variants have been identified in subjects with obsessive-compulsive disorder (OCD) and autism spectrum disorder (ASD) that impact transporter phosphorylation, cell surface trafficking and/or conformational dynamics. Prior to an initial description of a novel mouse line expressing the non-phosphorylatable SERT substitution Thr276Ala, we review efforts made to elucidate the structure and conformational dynamics of SERT with a focus on research implicating phosphorylation at Thr276 as a determinant of SERT conformational dynamics. Read More

View Article and Full-Text PDF

Alginate-Derived Mannuronate Oligosaccharide Attenuates Tauopathy through Enhancing Autophagy.

J Agric Food Chem 2021 Apr 8. Epub 2021 Apr 8.

Shenzhen Key Laboratory of Marine Bioresources and Ecology, and Guangdong Provincial Key Laboratory for Plant Epigenetics, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, PR China.

Polymannuronate (PM) is an acidic polysaccharide prepared from alginate, contained in edible brown seaweeds. An unsaturated mannuronate oligosaccharide (MOS) is an enzymatically depolymerized oligosaccharide prepared from PM. The effects of MOS on attenuating tauopathy were studied in HEK293/Tau cells and primary triple transgenic (3×Tg) neurons. Read More

View Article and Full-Text PDF

Comparative Studies in the A30P and A53T α-Synuclein Strains to Investigate the Molecular Origins of Parkinson's Disease.

Front Cell Dev Biol 2021 22;9:552549. Epub 2021 Mar 22.

Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge, Cambridge, United Kingdom.

The aggregation of α-synuclein is a hallmark of Parkinson's disease (PD) and a variety of related neurological disorders. A number of mutations in this protein, including A30P and A53T, are associated with familial forms of the disease. Patients carrying the A30P mutation typically exhibit a similar age of onset and symptoms as sporadic PD, while those carrying the A53T mutation generally have an earlier age of onset and an accelerated progression. Read More

View Article and Full-Text PDF

Opinion on the Use of Animal Models in Nonclinical Safety Assessment: Pros and Cons.

Toxicol Pathol 2021 Apr 8:1926233211003498. Epub 2021 Apr 8.

StageBio, Castle Dr, Mason, OH, USA.

Nonclinical evaluation of human safety risks for new chemical entities (NCEs) is primarily conducted in conventional healthy animals (CHAs); however, in certain instances, animal models of diseases (AMDs) can play a critical role in the understanding of human health risks. Animal models of diseases may be especially important when there is a need to understand how disease conditions associated with the intended indication might impact risk assessment of NCEs or when CHAs lack the human-specific target of interest (receptor, etc). Although AMDs have potential benefits over CHAs, they also have limitations. Read More

View Article and Full-Text PDF

Genome editing in fruit, ornamental, and industrial crops.

Transgenic Res 2021 Apr 6. Epub 2021 Apr 6.

Department of Horticulture, Washington State University, Pullman, WA, USA.

The advent of genome editing has opened new avenues for targeted trait enhancement in fruit, ornamental, industrial, and all specialty crops. In particular, CRISPR-based editing systems, derived from bacterial immune systems, have quickly become routinely used tools for research groups across the world seeking to edit plant genomes with a greater level of precision, higher efficiency, reduced off-target effects, and overall ease-of-use compared to ZFNs and TALENs. CRISPR systems have been applied successfully to a number of horticultural and industrial crops to enhance fruit ripening, increase stress tolerance, modify plant architecture, control the timing of flower development, and enhance the accumulation of desired metabolites, among other commercially-important traits. Read More

View Article and Full-Text PDF

Age-related changes in NG2-expressing telocytes of rat stomach.

PLoS One 2021 6;16(4):e0249729. Epub 2021 Apr 6.

Laboratory for Cellular Function Imaging, RIKEN Center for Biosystems Dynamics Research, Chuo-ku, Kobe, Japan.

NG2 immunoreactive cells (NG2 cells) are found in the brain and peripheral tissues including the skin, intestinal tracts, and bladder. In a previous study, we observed the presence of NG2 cells in the stomach using bioluminescence imaging techniques in NG2-firefly luciferase (fLuc) transgenic (Tg) rats. Here, we aimed to identify and characterize NG2 cells in the adult rat stomach. Read More

View Article and Full-Text PDF

IntEResting structures: formation and applications of organized smooth endoplasmic reticulum in plant cells.

Plant Physiol 2021 Apr;185(3):550-561

Department of Plant Sciences, University of Oxford, Oxford OX1 3RB, UK.

The endoplasmic reticulum (ER) is an organelle with remarkable plasticity, capable of rapidly changing its structure to accommodate different functions based on intra- and extracellular cues. One of the ER structures observed in plants is known as "organized smooth endoplasmic reticulum" (OSER), consisting of symmetrically stacked ER membrane arrays. In plants, these structures were first described in certain specialized tissues, e. Read More

View Article and Full-Text PDF