269,203 results match your criteria transgenic mouse

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

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Beclin-1 overexpression regulates NLRP3 activation by promoting TNFAIP3 in microvascular injury following myocardial reperfusion.

Cell Signal 2021 Apr 10:110008. Epub 2021 Apr 10.

Department of Technology Transfer Center, Kunming Medical University, Kunming 650500, China. Electronic address:

Innate immune response contributes significantly to ischemia reperfusion (I/R) injury. Targeting innate immunity seems to be a promising method for protecting the microvascular injury in ST-elevation myocardial infarction (STEMI) patients following myocardial I/R injury (MI/R). NLRP3 inflammasome is a central part of the innate immune system involved in the pathophysiological process of MI/R. Read More

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DNA methylome, transcriptome, and prostate cancer prevention by phenethyl isothiocyanate in TRAMP mice.

Mol Carcinog 2021 Apr 13. Epub 2021 Apr 13.

Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers-The State University of New Jersey, Piscataway, New Jersey, USA.

Epigenetics/epigenomics has been shown to be involved in carcinogenesis. However, how the epigenome would be altered in the transgenic adenocarcinoma of the mouse prostate (TRAMP) cancer model and the effect of cancer chemopreventive phytochemical phenethyl isothiocyanate (PEITC) on the epigenome in TRAMP mice are not known. PEITC has been reported to reduce the risk of many cancers including prostate cancer (PCa). Read More

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Serial intravital imaging captures dynamic and functional endothelial remodeling with single-cell resolution.

JCI Insight 2021 Apr 13. Epub 2021 Apr 13.

Department of Physiology and Neuroscience, University of Southern California, Los Angeles, United States of America.

Endothelial cells are important in the maintenance of healthy blood vessels and in the development of vascular diseases. However, the origin and dynamics of endothelial precursors and remodeling at the single-cell level have been difficult to study in vivo due to technical limitations. We aimed to develop a direct visual approach to track the fate and function of single endothelial cells over several days-weeks in the same vascular bed in vivo using multiphoton microscopy (MPM) of transgenic Cdh5-Confetti mice and the kidney glomerulus as a model. Read More

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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

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The association of enteric neuropathy with gut phenotypes in acute and progressive models of Parkinson's disease.

Sci Rep 2021 Apr 12;11(1):7934. Epub 2021 Apr 12.

Department of Medicine, Western Health, Melbourne University, Sunshine, VIC, 3021, Australia.

Parkinson's disease (PD) is associated with neuronal damage in the brain and gut. This work compares changes in the enteric nervous system (ENS) of commonly used mouse models of PD that exhibit central neuropathy and a gut phenotype. Enteric neuropathy was assessed in five mouse models: peripheral injection of MPTP; intracerebral injection of 6-OHDA; oral rotenone; and mice transgenic for A53T variant human α-synuclein with and without rotenone. Read More

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Therapeutic B-cell depletion reverses progression of Alzheimer's disease.

Nat Commun 2021 04 12;12(1):2185. Epub 2021 Apr 12.

Immunoregulation Section, Laboratory of Immunology and Molecular Biology, National Institute on Aging, Baltimore, MD, USA.

The function of B cells in Alzheimer's disease (AD) is not fully understood. While immunoglobulins that target amyloid beta (Aβ) may interfere with plaque formation and hence progression of the disease, B cells may contribute beyond merely producing immunoglobulins. Here we show that AD is associated with accumulation of activated B cells in circulation, and with infiltration of B cells into the brain parenchyma, resulting in immunoglobulin deposits around Aβ plaques. Read More

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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

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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

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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

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Efficiency comparison of B6(Cg)-Tyr /J and C57BL/6NTac embryos as hosts for the generation of knockout mice.

Transgenic Res 2021 Apr 12. Epub 2021 Apr 12.

CAM-SU Genomic Resource Center, Soochow University, Suzhou, 215123, Jiang Su, China.

Careful selection of the host embryo is critical to the efficient production of knockout (KO) mice when injecting mouse embryonic stem (mES) cells into blastocysts. B6(Cg)-Tyr/J (B6 albino) and C57BL/6NTac (B6NTac) strains of mice are widely used to produce host blastocysts for such procedures. Here, we tested these two strains to identify an appropriate match for modified agouti C57BL/6N (JM8A3. Read More

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An Orthotopic Mouse Model of Ovarian Cancer using Human Stroma to Promote Metastasis.

J Vis Exp 2021 Mar 23(169). Epub 2021 Mar 23.

Division of Hematology/Oncology, Department of Medicine, Hillman Cancer Center, University of Pittsburgh; Division of Gynecologic Oncology, Department of Obstetrics, Gynecology, and Reproductive Sciences, Magee-Womens' Hospital, University of Pittsburgh Medical Center;

Ovarian cancer is characterized by early, diffuse metastasis with 70% of women having metastatic disease at the time of diagnosis. While elegant transgenic mouse models of ovarian cancer exist, these mice are expensive and take a long time to develop tumors. Intraperitoneal injection xenograft models lack human stroma and do not accurately model ovarian cancer metastasis. Read More

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Dissection of the Endolymphatic Sac from Mice.

J Vis Exp 2021 Mar 29(169). Epub 2021 Mar 29.

Otolaryngology Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health;

The study of mutant mouse models of human hearing and balance disorders has unraveled many structural and functional changes which may contribute to the human phenotypes. Although important progress has been done in the understanding of the development and function of the neurosensory epithelia of the cochlea and vestibula, limited knowledge is available regarding the development, cellular composition, molecular pathways and functional characteristics of the endolymphatic sac. This is, in large part, due to the difficulty of visualizing and microdissecting this tissue, which is an epithelium comprised of only one cell layer. Read More

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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

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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

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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

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Neuronal tau species transfer to astrocytes and induce their loss according to tau aggregation state.

Brain 2021 Apr 11. Epub 2021 Apr 11.

Université Paris-Saclay, CEA, CNRS, MIRCen, Laboratoire des Maladies Neurodégénératives, 92265, Fontenay-aux-Roses, France.

Deposits of different abnormal forms of tau in neurons and astrocytes represent key anatomo-pathological features of tauopathies. Although tau protein is highly enriched in neurons and poorly expressed by astrocytes, the origin of astrocytic tau is still elusive. Here, we used innovative gene transfer tools to model tauopathies in adult mouse brains and to investigate the origin of astrocytic tau. Read More

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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

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Advances in Rodent Models for Breast Cancer Formation, Progression, and Therapeutic Testing.

Front Oncol 2021 26;11:593337. Epub 2021 Mar 26.

Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China.

Breast cancer is a highly complicated disease. Advancement in the treatment and prevention of breast cancer lies in elucidation of the mechanism of carcinogenesis and progression. Rodent models of breast cancer have developed into premier tools for investigating the mechanisms and genetic pathways in breast cancer progression and metastasis and for developing and evaluating clinical therapeutics. Read More

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Tolerance to Proinsulin-1 Reduces Autoimmune Diabetes in NOD Mice.

Front Immunol 2021 25;12:645817. Epub 2021 Mar 25.

St. Vincent's Institute, Fitzroy, VIC, Australia.

T-cell responses to insulin and its precursor proinsulin are central to islet autoimmunity in humans and non-obese diabetic (NOD) mice that spontaneously develop autoimmune diabetes. Mice have two proinsulin genes proinsulin -1 and 2 that are differentially expressed, with predominant proinsulin-2 expression in the thymus and proinsulin-1 in islet beta-cells. In contrast to proinsulin-2, proinsulin-1 knockout NOD mice are protected from autoimmune diabetes. Read More

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20()-protopanaxadiol and oleanolic acid ameliorate cognitive deficits in APP/PS1 transgenic mice by enhancing hippocampal neurogenesis.

J Ginseng Res 2021 Mar 16;45(2):325-333. Epub 2020 Jul 16.

Department of Biology, Faculty of Science, Hong Kong Baptist University (HKBU), Kowloon Tong, Hong Kong Special Administrative Region (HKSAR), China.

Background: Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders. Enhancing hippocampal neurogenesis by promoting proliferation and differentiation of neural stem cells (NSCs) is a promising therapeutic strategy for AD. 20()-protopanaxadiol (PPD) and oleanolic acid (OA) are small, bioactive compounds found in ginseng that can promote NSC proliferation and neural differentiation . Read More

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Female dominance of both spatial cognitive dysfunction and neuropsychiatric symptoms in a mouse model of Alzheimer's disease.

Exp Anim 2021 Apr 9. Epub 2021 Apr 9.

Department of Immunology and Medicine, St. Marianna University of School of Medicine.

Alzheimer's disease (AD) is a prevalent neurological disorder affecting memory function in elderly persons. Indeed, AD exhibits abnormality in cognitive behaviors and higher susceptibility to neuropsychiatric symptoms (NPS). Various factors including aging, sex difference and NPS severity, are implicated during in development of AD. Read More

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Local Action of Neprilysin Exacerbates Pressure Overload Induced Cardiac Remodeling.

Hypertension 2021 Apr 12:HYPERTENSIONAHA12016445. Epub 2021 Apr 12.

Cardiovascular Medicine, Nara Medical University, Nara, Japan (H.N., T.K., K.O., Y.N., T. Nakano, S.I., T.U., A.S., T. Nishida, T.S., S.O., M.W., R.K., Y.S.).

NEP (Neprilysin) degrades natriuretic peptides, and its inhibition is a clinically accepted target for heart failure treatment. NEP is widely expressed in various organs, including the heart. However, the pathophysiological significance of local cardiac NEP is not fully understood. Read More

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Protective Effects of a Small Molecule Inhibitor, DDQ Against Amyloid Beta in Alzheimer's Disease.

Mitochondrion 2021 Apr 8. Epub 2021 Apr 8.

Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA; Neuroscience & Pharmacology, Texas Tech University Health Sciences Center, Lubbock, TX, USA; Neurology, Departments of School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA; Public Health Department of Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX, USA; Department of Speech, Language and Hearing Sciences, School Health Professions, Texas Tech University Health Sciences Center, Lubbock, TX, USA. Electronic address:

The purpose of our study is to determine the protective effects of the newly discovered molecule DDQ (diethyl (3,4-dihydroxyphenethylamino)(quinolin-4-yl) methylphosphonate) against mutant APP and amyloid-beta (Aβ) in Alzheimer's disease (AD). To achieve our objective, we used a well characterized amyloid-beta precursor protein (APP) transgenic mouse model (Tg2576 strain). We administered DDQ, a 20 mg/kg body weight (previously determined in our laboratory) intra-peritoneally 3-times per week for 2 months, starting at the beginning of the 12 month, until the end of the 14 month. Read More

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Mannan oligosaccharide attenuates cognitive and behavioral disorders in the 5xFAD Alzheimer's disease mouse model via regulating the gut microbiota-brain axis.

Brain Behav Immun 2021 Apr 9. Epub 2021 Apr 9.

Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi, China; Department of Food Science, Cornell University, Ithaca, New York, 14853, United States. Electronic address:

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive deficits and psychiatric symptoms. The gut microbiota-brain axis plays a pivotal role during AD development, which could target nutritional intervention. The prebiotic mannan oligosaccharide (MOS) has been reported to reshape the gut microbiome and enhanced the formation of the neuroprotective metabolites short-chain fatty acids (SCFAs). Read More

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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

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GILT in tumor cells improves T cell-mediated anti-tumor immune surveillance.

Immunol Lett 2021 Apr 7. Epub 2021 Apr 7.

Department of Biochemistry and Molecular Biology, Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China; Key Laboratory of Immune Microenvironment and Disease, Ministry of Education, Key Laboratory of Cellular and Molecular Immunology in Tianjin, Excellent Talent Project, Tianjin Medical University, Tianjin, China. Electronic address:

The lysosomal thiol reductase GILT catalyzes the reduction of disulfide bonds of protein antigens, facilitating antigen-presenting cells (APCs) to present antigen to T cells. However, whether GILT expression in tumor cells can be associated with improved T cell-mediated anti-tumor responses remains unknown. Here, we identify that GILT is able to facilitate anti-tumor immune surveillance via promoting MHC class I mediated-antigen presentation in colon carcinoma. Read More

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Increased toxicity and retention of Perflourooctane Sulfonate (PFOS) in humanized CYP2B6-Transgenic mice compared to Cyp2b-null mice is relieved by a High-Fat Diet (HFD).

Food Chem Toxicol 2021 Apr 7:112175. Epub 2021 Apr 7.

Environmental Toxicology Program, Clemson University, Clemson, SC, 29634. Electronic address:

PFOS is a persistent, fluorosurfactant used in multiple products. Murine Cyp2b's are induced by PFOS and high-fat diets (HFD) and therefore we hypothesized that human CYP2B6 may alleviate PFOS-induced steatosis. Cyp2b-null and hCYP2B6-Tg mice were treated with 0, 1, or 10mg/kg/day PFOS by oral gavage for 21-days while provided a chow diet (ND) or HFD. Read More

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Ultrasmall Copper (I) Sulfide Nanoparticles Block Hepatitis B Virus.

Angew Chem Int Ed Engl 2021 Apr 10. Epub 2021 Apr 10.

Jiangnan University, School of Food Science and Technology, lihu road 1800#, 214122, Wuxi, CHINA.

Hepatitis B virus (HBV) poses a severe threat to public health and social development. Here, we synthesized 4 ± 0.5 nm copper (I) sulfide (Cu 2 S) nanoparticles (NPs) with 46 mdeg chiroptical properties at 530 nm to selectively cleavage HBV core antigen (HBcAg) and effectively blocked HBV assembly and prevented HBV infection both in vitro and in vivo under light at 808 nm. Read More

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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

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