268,107 results match your criteria transgenic mice

Berberine Improves Behavioral and Cognitive Deficits in a Mouse Model of Alzheimer's Disease via Regulation of β-Amyloid Production and Endoplasmic Reticulum Stress.

ACS Chem Neurosci 2021 May 13. Epub 2021 May 13.

Department of Neurology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by βamyloid (Aβ), neurofibrillary tangles, and neuronal cell death. Aggressive Aβ accumulation accelerates senile plaque formation and perturbs endoplasmic reticulum (ER) function. Aβ accumulation-induced changes stimulate the unfolded protein response (UPR), which can trigger neuronal apoptosis. Read More

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Inactivation of the CB receptor accelerated the neuropathological deterioration in TDP-43 transgenic mice, a model of amyotrophic lateral sclerosis.

Brain Pathol 2021 May 13:e12972. Epub 2021 May 13.

Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Investigación en Neuroquímica, Universidad Complutense, Madrid, Spain.

The activation of the cannabinoid receptor type-2 (CB ) afforded neuroprotection in amyotrophic lateral sclerosis (ALS) models. The objective of this study was to further investigate the relevance of the CB receptor through investigating the consequences of its inactivation. TDP-43(A315T) transgenic mice were crossed with CB receptor knock-out mice to generate double mutants. Read More

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Decrease in Skin Prion-Seeding Activity of Prion-Infected Mice Treated with a Compound Against Human and Animal Prions: a First Possible Biomarker for Prion Therapeutics.

Mol Neurobiol 2021 May 13. Epub 2021 May 13.

Departments of Pathology and Neurology, Case Western Reserve University School of Medicine, Cleveland, OH, 44106, USA.

Previous studies have revealed that the infectious scrapie isoform of prion protein (PrP) harbored in the skin tissue of patients or animals with prion diseases can be amplified and detected through the serial protein misfolding cyclic amplification (sPMCA) or real-time quaking-induced conversion (RT-QuIC) assays. These findings suggest that skin PrP-seeding activity may serve as a biomarker for the diagnosis of prion diseases; however, its utility as a biomarker for prion therapeutics remains largely unknown. Cellulose ethers (CEs, such as TC-5RW), widely used as food and pharmaceutical additives, have recently been shown to prolong the lifespan of prion-infected mice and hamsters. Read More

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Long-term effect of human mini-dystrophin in transgenic mdx mice improves muscle physiological function.

FASEB J 2021 Jun;35(6):e21628

Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, USA.

Duchenne muscular dystrophy (DMD) is a lethal genetic muscle disorder caused by recessive mutations in dystrophin gene, affecting 1/3000 males. Gene therapy has been proven to ameliorate dystrophic pathology. To investigate therapeutic benefits from long-term effect of human mini-dystrophin and functional outcomes, transgenic mdx mice (Tg-mdx) containing a single copy of human mini-dystrophin (∆hDys3849) gene, five rods (Rods1-2, Rods22-24), and two hinges (H1 and H4) driven by a truncated creatine-kinase promoter (dMCK) in a recombinant adeno-associated viral vector (rAAV) backbone, were generated and used to determine gene expression and improvement of muscle function. Read More

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Synapsin-caveolin-1 gene therapy preserves neuronal and synaptic morphology and prevents neurodegeneration in a mouse model of AD.

Mol Ther Methods Clin Dev 2021 Jun 29;21:434-450. Epub 2021 Mar 29.

Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.

Alzheimer's disease (AD) is the most common form of neurodegeneration and cognitive dysfunction in the elderly. Identifying molecular signals that mitigate and reverse neurodegeneration in AD may be exploited therapeutically. Transgenic AD mice (PSAPP) exhibit learning and memory deficits at 9 and 11 months, respectively, with associated decreased expression of caveolin-1 (Cav-1), a membrane/lipid raft (MLR) scaffolding protein necessary for synaptic and neuroplasticity. Read More

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Lentivirus-Carried microRNA-195 Rescues Memory Deficits of Alzheimer's Disease Transgenic Mouse by Attenuating the Generation of Amyloid Plaques.

Front Pharmacol 2021 26;12:633805. Epub 2021 Apr 26.

Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy of Harbin Medical University, Harbin, China.

Although lots of new drugs are developed to treat Alzheimer's disease (AD), many clinical trials of monotherapy have failed to affect disease progression or symptoms compared with placebo. Recently, scientists believe that combination treatment is more promising than monotherapy. Previous studies found that microRNA-195 () was down-regulated in the hippocampi and cortices of chronic brain hypoperfusion (CBH) rats and ApoE4 mice, and up-regulation of can improve the declined cognitive function of ApoE4 mice and CBH rats by targeting multi-genes that are related to AD pathology, including amyloid precursor protein (APP) and β-site APP cleaving enzyme 1 (BACE1) genes. Read More

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Cancer-associated fibroblasts in pancreatic ductal adenocarcinoma determine response to SLC7A11 inhibition.

Cancer Res 2021 May 12. Epub 2021 May 12.

Personalised Cancer Therapeutics, Cancer Division, The Kinghorn Cancer Centre, The Garvan Institute of Medical Research.

Cancer-Associated Fibroblasts (CAF) are major contributors to pancreatic ductal adenocarcinoma (PDAC) progression through pro-tumor signaling and the generation of fibrosis that creates a physical barrier to drugs. CAF inhibition is thus an ideal component of any therapeutic approach for PDAC. SLC7A11, a cystine transporter, has been identified as a potential therapeutic target in PDAC cells. Read More

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Antibody semorinemab reduces tau pathology in a transgenic mouse model and engages tau in patients with Alzheimer's disease.

Sci Transl Med 2021 May;13(593)

Department of Pathology, Genentech Inc., San Francisco, CA 94080, USA.

Tau has become an attractive alternative target for passive immunotherapy efforts for Alzheimer's disease (AD). The anatomical distribution and extent of tau pathology correlate with disease course and severity better than other disease markers to date. We describe here the generation, preclinical characterization, and phase 1 clinical characterization of semorinemab, a humanized anti-tau monoclonal antibody with an immunoglobulin G4 (igG4) isotype backbone. Read More

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TREM2 promotes natural killer cell development in CD3CD122NK1.1 pNK cells.

BMC Immunol 2021 May 12;22(1):30. Epub 2021 May 12.

Department of Predictive Toxicology, Korea Institute of Toxicology, 141 Gajeong-ro, Yuseong-gu, Daejeon, 34114, Republic of Korea.

Background: Triggering receptor expressed on myeloid cells 2 (TREM2) signaling is considered to regulate anti-inflammatory responses in macrophages, dendritic cell maturation, osteoclast development, induction of obesity, and Alzheimer's disease pathogenesis. However, little is known regarding the effect of TREM2 on natural killer (NK) cells.

Results: Here, we demonstrated for the first time that CD3CD122NK1. Read More

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Interferon signaling suppresses the unfolded protein response and induces cell death in hepatocytes accumulating hepatitis B surface antigen.

PLoS Pathog 2021 May 12;17(5):e1009228. Epub 2021 May 12.

Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Virus infection, such as hepatitis B virus (HBV), occasionally causes endoplasmic reticulum (ER) stress. The unfolded protein response (UPR) is counteractive machinery to ER stress, and the failure of UPR to cope with ER stress results in cell death. Mechanisms that regulate the balance between ER stress and UPR are poorly understood. Read More

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Multiple system atrophy-associated oligodendroglial protein p25α stimulates formation of novel α-synuclein strain with enhanced neurodegenerative potential.

Acta Neuropathol 2021 May 12. Epub 2021 May 12.

DANDRITE, Danish Research Institute of Translational Neuroscience & Department of Biomedicine, Aarhus University, 8000, Aarhus C, Denmark.

Pathology consisting of intracellular aggregates of alpha-Synuclein (α-Syn) spread through the nervous system in a variety of neurodegenerative disorders including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. The discovery of structurally distinct α-Syn polymorphs, so-called strains, supports a hypothesis where strain-specific structures are templated into aggregates formed by native α-Syn. These distinct strains are hypothesised to dictate the spreading of pathology in the tissue and the cellular impact of the aggregates, thereby contributing to the variety of clinical phenotypes. Read More

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Toxicological and anti-tumor effects of a linden extract ( Scop.) in a HPV16-transgenic mouse model.

Food Funct 2021 May;12(9):4005-4014

Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Inov4Agro, University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal.

Tilia platyphyllos Scop. is a popular broad-leaved tree, native to Central and Southern Europe. Hydroethanolic extracts rich in phenolic compounds obtained from T. Read More

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Gout-induced endothelial impairment: The role of SREBP2 transactivation of YAP.

FASEB J 2021 Jun;35(6):e21613

Department of General Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Gout is a multifaceted inflammatory disease involving vascular impairments induced by hyperuricemia. Experiments using human umbilical vein endothelial cells treated with uric acid (UA), monosodium urate (MSU), or serum from gout patients showed increased expression of pro-inflammatory genes (ie, VCAM1, ICAM1, CYR61, CCNA1, and E2F1) with attendant increase in monocyte adhesion. Mechanistically, UA- or MSU-induced SREBP2 expression and its transcriptional activity. Read More

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Ras GEF Mouse Models for the Analysis of Ras Biology and Signaling.

Methods Mol Biol 2021 ;2262:361-395

Centro de Investigación del Cáncer-Instituto de Biología Molecular y Celular del Cáncer (CSIC-Universidad de Salamanca) and CIBERONC, Salamanca, Spain.

Animal models have become in recent years a crucial tool to understand the physiological and pathological roles of many cellular proteins. They allow analysis of the functional consequences of [1] complete or partial (time- or organ-limited) removal of specific proteins (knockout animals), [2] the exchange of a wild-type allele for a mutant or truncated version found in human illnesses (knock-in), or [3] the effect of overexpression of a given protein in the whole body or in specific organs (transgenic mice). In this regard, the study of phenotypes in Ras GEF animal models has allowed researchers to find specific functions for otherwise very similar proteins, uncovering their role in physiological contexts such as memory formation, lymphopoiesis, photoreception, or body homeostasis. Read More

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January 2021

Upregulated expression of a subset of genes in ;/ mice: Evidence of an interaction between diabetes-linked obesity and Alzheimer's disease.

FASEB Bioadv 2021 May 2;3(5):323-333. Epub 2021 Mar 2.

Department of Aging Neurobiology Center for Development of Advanced Medicine for Dementia National Center for Geriatrics and Gerontology Obu Aichi Japan.

Clinical studies have indicated that obesity and diabetes are associated with Alzheimer's disease (AD) and neurodegeneration. However, the mechanism by which obesity/diabetes and AD interact with each other and contribute to dementia remains elusive. To obtain insights into their interaction at molecular levels, we performed gene expression analysis of ;/ mice, which were generated by crossing transgenic AD model mice (APP23 mice) with / mice, which are obese and mildly diabetic. Read More

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LBSL: Case Series and DARS2 Variant Analysis in Early Severe Forms With Unexpected Presentations.

Neurol Genet 2021 Apr 2;7(2):e559. Epub 2021 Feb 2.

Department of Child Neurology, Emma Childrens Hospital, Amsterdam University Medical Centers, Vrije Universiteit and Amsterdam Neuroscience, The Netherlands (M.D.S., T.E.M.A.); Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Italy (S.F., C.D., P.G.); Area di Ricerca Genetica e Malattie Rare (E.B.), Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy; Laboratory of Oncology and Molecular Genetics (K.A.), Clínica las Condes, Santiago, Chile; Department of Pediatric Neurology (C.C.), Clínica Las Condes, Santiago, Chile; Division of Child Neurology (P.T.), Department of Neurology, Istanbul Faculty of Medicine, Turkey; Department of Paediatrics (C.A.S.), Royal Childrens Hospital, Murdoch Childrens Research Institute and University of Melbourne, Victoria, Australia; Pediatric Neurology (C.E.E.), Radboud University Medical Center, Amalia Childrens Hospital, Nijmegen, The Netherlands; Department of Pediatrics (A.S.-V.), University of South Florida, Tampa; Unit of Pediatric Neurology and Neurorehabilitation (S.L.), Department WomanMother-Child, Lausanne University Hospital, Switzerland; Community Pediatrics, Royal Berkshire Hospital, Reading (S.H.), United Kingdom; Neuropediatric Department (T.S.-M.), Childrens Hospital, Luzern, Switzerland; Unit of Neurorehabilitation (G.V.), Department of Neurosciences, Bambino Gesù Children's Research Hospital, IRCCS, Rome, Italy; Paediatric Neurology (G.C.), Nottingham Childrens Hospital, United Kingdom; PEDEGO Research Unit (E.R.), Medical Research Center and Department of Clinical Genetics, University of Oulu and Oulu University Hospital, Finland; Radiology (C.O.), Clínica las Condes, Santiago, Chile; Unit of Neuromuscular and Neurodegenerative Disorders (E.S.B), Area di Ricerca Genetica e Malattie Rare and Department of Neurosciences, Bambino Gesù Children's Research Hospital, IRCCS, Rome, Italy; and Department of Child Neurology (M.S.v.d.K.), Emma Childrens Hospital and Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University, Amsterdam, the Netherlands.

Objective: Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is regarded a relatively mild leukodystrophy, diagnosed by characteristic long tract abnormalities on MRI and biallelic variants in , encoding mitochondrial aspartyl-tRNA synthetase (mtAspRS). variants in LBSL are almost invariably compound heterozygous; in 95% of cases, 1 is a leaky splice site variant in intron 2. A few severely affected patients, still fulfilling the MRI criteria, have been described. Read More

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Enhanced differentiation of functional human T cells in NSGW41 mice with tissue-specific expression of human interleukin-7.

Leukemia 2021 May 11. Epub 2021 May 11.

Institute for Molecular Medicine, Goethe University Frankfurt am Main, Frankfurt am Main, Germany.

Humanized mouse models have become increasingly valuable tools to study human hematopoiesis and infectious diseases. However, human T-cell differentiation remains inefficient. We generated mice expressing human interleukin-7 (IL-7), a critical growth and survival factor for T cells, under the control of murine IL-7 regulatory elements. Read More

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Portable bioluminescent platform for in vivo monitoring of biological processes in non-transgenic animals.

Nat Commun 2021 May 11;12(1):2680. Epub 2021 May 11.

Institute of Chemical Sciences and Engineering (ISIC), Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.

Bioluminescent imaging (BLI) is one of the most powerful and widely used preclinical imaging modalities. However, the current technology relies on the use of transgenic luciferase-expressing cells and animals and therefore can only be applied to a limited number of existing animal models of human disease. Here, we report the development of a "portable bioluminescent" (PBL) technology that overcomes most of the major limitations of traditional BLI. Read More

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Diffusion Tensor Imaging Reveals Whole-Brain Microstructural Changes in the P301L Mouse Model of Tauopathy.

Neurodegener Dis 2021 May 11:1-12. Epub 2021 May 11.

Institute for Biomedical Engineering, ETH & University of Zurich, Zurich, Switzerland.

Introduction: Increased expression of hyperphosphorylated tau and the formation of neurofibrillary tangles are associated with neuronal loss and white matter damage. Using high-resolution ex vivo diffusion tensor imaging (DTI), we investigated microstructural changes in the white and grey matter in the P301L mouse model of human tauopathy at 8.5 months of age. Read More

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JWX-A0108, a positive allosteric modulator of α7 nAChR, attenuates cognitive deficits in APP/PS1 mice by suppressing NF-κB-mediated inflammation.

Int Immunopharmacol 2021 May 8;96:107726. Epub 2021 May 8.

Department of Pharmacology, Qingdao University School of Pharmacy, Qingdao 266000, China. Electronic address:

Neuroinflammation plays an early and prominent role in the pathology of Alzheimer's disease (AD). Studies have shown that cholinergic lesion is a contributor for the pathophysiology of AD. The α7 nicotinic acetylcholine receptors (nAChRs), a subtype of nAChRs, are abundantly expressed in the brain regions related to cognition and memory, such as hippocampus and frontal cortex. Read More

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Shenqi Yizhi Granule attenuates Aβ induced cognitive dysfunction via inhibiting JAK2/STAT3 activated astrocyte reactivity.

Exp Gerontol 2021 May 8:111400. Epub 2021 May 8.

Institute of Meterial Medica Integration and Transformation for Brain Disorders, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China; School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, PR China. Electronic address:

Shenqi Yizhi Granule (SYG), a modern preparation herbs based on the theory of traditional Chinese medicine, has been proved to be effective against Alzheimer's disease in clinical trials, APP/PS1 mice and 5XFAD transgenic mice. But the underlying mechanism remains ambiguous. Increasing evidence supports the crucial role of astrocyte reactivity in the pathogenesis of Alzheimer's disease (AD). Read More

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Microglial NLRP3 inflammasome activation promotes prolactinomas development.

Endocr Relat Cancer 2021 May 1. Epub 2021 May 1.

X Guo, Department of Pharmacology, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Shandong University, Jinan, China.

Prolactinomas have harmful effects on human health, and 25% of prolactinoma patients do not respond to the therapy of dopamine receptor agonist in the clinic. Thus, it is important to reveal the pathogenesis and develop new therapeutic methods for prolactinomas. Herein, two animal models of prolactinomas, namely oestrogen-treated rats and transgenic D2 dopamine receptor-deficient mice, were used. Read More

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A novel highly potent inhibitor of TMPRSS2-like proteases blocks SARS-CoV-2 variants of concern and is broadly protective against infection and mortality in mice.

bioRxiv 2021 May 4. Epub 2021 May 4.

The COVID-19 pandemic caused by the SARS-CoV-2 virus remains a global public health crisis. Although widespread vaccination campaigns are underway, their efficacy is reduced against emerging variants of concern (VOCs) . Development of host-directed therapeutics and prophylactics could limit such resistance and offer urgently needed protection against VOCs . Read More

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Symmetry breaking of tissue mechanics in wound induced hair follicle regeneration of laboratory and spiny mice.

Nat Commun 2021 May 10;12(1):2595. Epub 2021 May 10.

Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

Tissue regeneration is a process that recapitulates and restores organ structure and function. Although previous studies have demonstrated wound-induced hair neogenesis (WIHN) in laboratory mice (Mus), the regeneration is limited to the center of the wound unlike those observed in African spiny (Acomys) mice. Tissue mechanics have been implicated as an integral part of tissue morphogenesis. Read More

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Pathomechanisms of ALS8: altered autophagy and defective RNA binding protein (RBP) homeostasis due to the VAPB P56S mutation.

Cell Death Dis 2021 May 10;12(5):466. Epub 2021 May 10.

Institute of Neuropathology, RWTH Aachen University Medical School, Pauwelsstr. 30, 52074, Aachen, Germany.

Mutations in RNA binding proteins (RBPs) and in genes regulating autophagy are frequent causes of familial amyotrophic lateral sclerosis (fALS). The P56S mutation in vesicle-associated membrane protein-associated protein B (VAPB) leads to fALS (ALS8) and spinal muscular atrophy (SMA). While VAPB is primarily involved in the unfolded protein response (UPR), vesicular trafficking and in initial steps of the autophagy pathway, the effect of mutant P56S-VAPB on autophagy regulation in connection with RBP homeostasis has not been explored yet. Read More

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The Pathological Role of Astrocytic MAOB in Parkinsonism Revealed by Genetic Ablation and Over-expression of MAOB.

Exp Neurobiol 2021 Apr;30(2):113-119

Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.

The cause of Parkinson's disease has been traditionally believed to be the dopaminergic neuronal death in the substantia nigra pars compacta (SNpc). This traditional view has been recently challenged by the proposal that reactive astrocytes serve as key players in the pathology of Parkinson's disease through excessive GABA release. This aberrant astrocytic GABA is synthesized by the enzymatic action of monoamine oxidase B (MAOB), whose pharmacological inhibition and gene-silencing are reported to significantly alleviate parkinsonian motor symptoms in animal models of Parkinson's disease. Read More

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Templated α-synuclein inclusion formation is independent of endogenous tau.

eNeuro 2021 May 10. Epub 2021 May 10.

Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, Birmingham, AL, USA 35294

Synucleinopathies including Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) are characterized by neuronal intracellular inclusions of α-synuclein (α-synuclein). Parkinson's disease dementia (PDD) and DLB are collectively the second most common cause of neurodegenerative dementia. In addition to associated inclusions, Lewy body diseases have dopaminergic neurodegeneration, motor defects and cognitive changes. Read More

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Heparanase overexpression impedes perivascular clearance of amyloid-β from murine brain: relevance to Alzheimer's disease.

Acta Neuropathol Commun 2021 May 10;9(1):84. Epub 2021 May 10.

Department of Medical Biochemistry and Microbiology, SciLifeLab Uppsala, University of Uppsala, The Biomedical Center Husargatan 3, Box 582, 751 23, Uppsala, Sweden.

Defective amyloid-β (Aβ) clearance from the brain is a major contributing factor to the pathophysiology of Alzheimer's disease (AD). Aβ clearance is mediated by macrophages, enzymatic degradation, perivascular drainage along the vascular basement membrane (VBM) and transcytosis across the blood-brain barrier (BBB). AD pathology is typically associated with cerebral amyloid angiopathy due to perivascular accumulation of Aβ. Read More

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Aβ43 aggregates exhibit enhanced prion-like seeding activity in mice.

Acta Neuropathol Commun 2021 May 10;9(1):83. Epub 2021 May 10.

Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Krembil Discovery Tower, Rm. 4KD481, 60 Leonard Ave., Toronto, ON, M5T 0S8, Canada.

When injected into genetically modified mice, aggregates of the amyloid-β (Aβ) peptide from the brains of Alzheimer's disease (AD) patients or transgenic AD mouse models seed cerebral Aβ deposition in a prion-like fashion. Within the brain, Aβ exists as a pool of distinct C-terminal variants with lengths ranging from 37 to 43 amino acids, yet the relative contribution of individual C-terminal Aβ variants to the seeding behavior of Aβ aggregates remains unknown. Here, we have investigated the relative seeding activities of Aβ aggregates composed exclusively of recombinant Aβ38, Aβ40, Aβ42, or Aβ43. Read More

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