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https://www.readbyqxmd.com/read/29149648/dried-plum-alleviates-symptoms-of-inflammatory-arthritis-in-tnf-transgenic-mice
#1
Faryal Mirza, Joseph Lorenzo, Hicham Drissi, Francis Y Lee, Do Y Soung
Dried plum (DP), a rich source of polyphenols has been shown to have bone-preserving properties in both animal models of osteoporosis and postmenopausal women. We evaluated if DP alleviated the destruction of joints in transgenic mice (TG) that overexpress human tumor necrosis factor (TNF), a genetic model of rheumatoid arthritis (RA). A four-week treatment of 20% DP diet in TG slowed the onset of arthritis and reduced bone erosions in the joints compared to TG on a regular diet. This was associated with fewer tartrate-resistant acid phosphatase (TRAP) positive cells, suggesting decreased osteoclastogenesis...
October 16, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/29149494/inhibiting-mt2-tfe3-dependent-autophagy-enhances-melatonin-induced-apoptosis-in-tongue-squamous-cell-carcinoma
#2
Tengfei Fan, Huifeng Pi, Min Li, Zhenhu Ren, Zhijing He, Feiya Zhu, Li Tian, Manyu Tu, Jia Xie, Mengyu Liu, Yuming Li, Miduo Tan, Gaoming Li, Weijia Qing, Russel J Reiter, Zhengping Yu, Hanjiang Wu, Zhou Zhou
Autophagy modulation is a potential therapeutic strategy for tongue squamous cell carcinoma (TSCC). Melatonin possesses significant anti-carcinogenic activity. However, whether melatonin induces autophagy and its roles in cell death in TSCC are unclear. Herein, we show that melatonin induced significant apoptosis in the TSCC cell line Cal27. Apart from the induction of apoptosis, we demonstrated that melatonin-induced autophagic flux in Cal27 cells as evidenced by the formation of GFP-LC3 puncta, and the upregulation of LC3-II and downregulation of SQSTM1/P62...
November 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/29146733/effects-of-chronically-increased-vegf-a-on-the-aging-heart
#3
Alexander G Marneros
Whether approaches to chronically increase VEGF-A in the heart may have beneficial effects and prevent the development of heart failure, in part by improving cardiac perfusion, or whether this increase could have detrimental effects on cardiac performance in the aging heart, has not been tested yet. In this study, a genetic mouse model with a chronic increase in VEGF-A in the heart is shown to have increased cardiac angiogenesis and develop cardiac hypertrophy with enhanced basal cardiac performance with age progression...
November 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29146705/complement-c3-is-a-novel-modulator-of-the-anti-fviii-immune-response
#4
Julie Rayes, Mathieu Ing, Sandrine Delignat, Ivan Peyron, Laurent Gilardin, Carl-Wilhelm Vogel, David C Fritzinger, Véronique Frémeaux-Bacchi, Srinivas V Kaveri, Lubka T Roumenina, Sébastien Lacroix-Desmazes
Development of neutralizing antibodies against therapeutic factor VIII (FVIII) is the most serious complication of the treatment of hemophilia A. Increasing evidence shows the multifactorial origin of the anti-FVIII immune response, combining both genetic and environmental factors. While a role for the complement system on innate as well as adaptive immunity has been documented, the implication of complement activation on the onset of the anti-FVIII immune response is unknown. Here, using in vitro assays for FVIII endocytosis by human monocyte-derived dendritic cells and presentation to T cells, as well as animal models of in vivo complement depletion, we show a novel role for complement C3 in enhancing the immune response against therapeutic FVIII...
November 16, 2017: Haematologica
https://www.readbyqxmd.com/read/29145128/microgravity-simulation-activates-cdc42-via-rap1gds1-to-promote-vascular-branch-morphogenesis-during-vasculogenesis
#5
Shouli Wang, Zhao Yin, Bei Zhao, Yanmei Qi, Jie Liu, Saum A Rahimi, Leonard Y Lee, Shaohua Li
Gravity plays an important role in normal tissue maintenance. The ability of stem cells to repair tissue loss in space through regeneration and differentiation remains largely unknown. To investigate the impact of microgravity on blood vessel formation from pluripotent stem cells, we employed the embryoid body (EB) model for vasculogenesis and simulated microgravity by clinorotation. We first differentiated mouse embryonic stem cells into cystic EBs containing two germ layers and then analyzed vessel formation under clinorotation...
November 7, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29143855/considerations-and-guidelines-for-mouse-metabolic-phenotyping-in-diabetes-research
#6
REVIEW
Thierry Alquier, Vincent Poitout
Mice are the most commonly used species in preclinical research on the pathophysiology of metabolic diseases. Although they are extremely useful for identifying pathways, mechanisms and genes regulating glucose and energy homeostasis, the specificities of the various mouse models and methodologies used to investigate a metabolic phenotype can have a profound impact on experimental results and their interpretation. This review aims to: (1) describe the most commonly used experimental tests to assess glucose and energy homeostasis in mice; (2) provide some guidelines regarding the design, analysis and interpretation of these tests, as well as for studies using genetic models; and (3) identify important caveats and confounding factors that must be taken into account in the interpretation of findings...
November 16, 2017: Diabetologia
https://www.readbyqxmd.com/read/29143824/pd-1-is-a-haploinsufficient-suppressor-of-t-cell-lymphomagenesis
#7
Tim Wartewig, Zsuzsanna Kurgyis, Selina Keppler, Konstanze Pechloff, Erik Hameister, Rupert Öllinger, Roman Maresch, Thorsten Buch, Katja Steiger, Christof Winter, Roland Rad, Jürgen Ruland
T cell non-Hodgkin lymphomas are a heterogeneous group of highly aggressive malignancies with poor clinical outcomes. T cell lymphomas originate from peripheral T cells and are frequently characterized by genetic gain-of-function variants in T cell receptor (TCR) signalling molecules. Although these oncogenic alterations are thought to drive TCR pathways to induce chronic proliferation and cell survival programmes, it remains unclear whether T cells contain tumour suppressors that can counteract these events...
November 15, 2017: Nature
https://www.readbyqxmd.com/read/29142736/strain-differences-in-cuprizone-induced-demyelination
#8
Qili Yu, Ryan Hui, Jiyoung Park, Yangyang Huang, Alexander W Kusnecov, Cheryl F Dreyfus, Renping Zhou
Background: Multiple sclerosis (MS) is a severe neurological disorder, characterized by demyelination of the central nervous system (CNS), and with a prevalence of greater than 2 million people worldwide. In terms of research in MS pathology, the cuprizone toxicity model is widely used. Here we investigated the contribution of genetic differences in response to cuprizone-induced demyelination in two genetically different mouse strains: CD1 and C57BL/6. Results: We demonstrate that exposure to a diet containing 0...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/29142232/tdp-43-misexpression-causes-defects-in-dendritic-growth
#9
Josiah J Herzog, Mugdha Deshpande, Leah Shapiro, Avital A Rodal, Suzanne Paradis
Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) share overlapping genetic causes and disease symptoms, and are linked neuropathologically by the RNA binding protein TDP-43 (TAR DNA binding protein-43 kDa). TDP-43 regulates RNA metabolism, trafficking, and localization of thousands of target genes. However, the cellular and molecular mechanisms by which dysfunction of TDP-43 contributes to disease pathogenesis and progression remain unclear. Severe changes in the structure of neuronal dendritic arbors disrupt proper circuit connectivity, which in turn could contribute to neurodegenerative disease...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29141886/pd-l1-genetic-overexpression-or-pharmacological-restoration-in-hematopoietic-stem-and-progenitor-cells-reverses-autoimmune-diabetes
#10
Moufida Ben Nasr, Sara Tezza, Francesca D'Addio, Chiara Mameli, Vera Usuelli, Anna Maestroni, Domenico Corradi, Silvana Belletti, Luca Albarello, Gabriella Becchi, Gian Paolo Fadini, Christian Schuetz, James Markmann, Clive Wasserfall, Leonard Zon, Gian Vincenzo Zuccotti, Paolo Fiorina
Immunologically based clinical trials performed thus far have failed to cure type 1 diabetes (T1D), in part because these approaches were nonspecific. Because the disease is driven by autoreactive CD4 T cells, which destroy β cells, transplantation of hematopoietic stem and progenitor cells (HSPCs) has been recently offered as a therapy for T1D. Our transcriptomic profiling of HSPCs revealed that these cells are deficient in programmed death ligand 1 (PD-L1), an important immune checkpoint, in the T1D nonobese diabetic (NOD) mouse model...
November 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29141867/host-resistance-to-endotoxic-shock-requires-the-neuroendocrine-regulation-of-group-1-innate-lymphoid-cells
#11
Linda Quatrini, Elisabeth Wieduwild, Sophie Guia, Claire Bernat, Nicolas Glaichenhaus, Eric Vivier, Sophie Ugolini
Upon infection, the immune system produces inflammatory mediators important for pathogen clearance. However, inflammation can also have deleterious effect on the host and is tightly regulated. Immune system-derived cytokines stimulate the hypothalamic-pituitary-adrenal (HPA) axis, triggering endogenous glucocorticoid production. Through interaction with ubiquitously expressed glucocorticoid receptors (GRs), this steroid hormone has pleiotropic effects on many cell types. Using a genetic mouse model in which the gene encoding the GR is selectively deleted in NKp46(+) innate lymphoid cells (ILCs), we demonstrated a major role for the HPA pathway in host resistance to endotoxin-induced septic shock...
November 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29140564/%C3%AE-catenin-and-il-1%C3%AE-dependent-cxcl10-production-drives-progression-of-disease-in-a-mouse-model-of-congenital-hepatic-fibrosis
#12
Eleanna Kaffe, Romina Fiorotto, Francesca Pellegrino, Valeria Mariotti, Mariangela Amenduni, Massimiliano Cadamuro, Luca Fabris, Mario Strazzabosco, Carlo Spirli
Congenital Hepatic Fibrosis (CHF), a genetic disease caused by mutations in the PKHD1 gene, encoding for the protein fibrocystin (FPC), is characterized by biliary dysgenesis, progressive portal fibrosis, and by a PKA-mediated activating phosphorylation of β-Catenin at Ser675. Biliary structures of Pkhd1(del4/del4) mice, a mouse model of CHF, secrete CXCL10 a chemokine able to recruit macrophages. The aim of this study is to clarify whether CXCL10 plays a pathogenetic role in disease progression in CHF/CD and to understand the mechanisms leading to increased CXCL10 secretion...
November 15, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29139535/contribution-of-cranial-neural-crest-cells-to-mouse-skull-development
#13
Taofen Wu, Guiqian Chen, Fei Tian, Hong-Xiang Liu
The mammalian skull vault is a highly regulated structure that evolutionally protects brain growth during vertebrate development. It consists of several membrane bones with different tissue origins (e.g. neural crest-derived frontal bone and mesoderm-derived parietal bone). Although membrane bones are formed through intramembranous ossification, the neural crest-derived frontal bone has superior capabilities for osteoblast activities and bone regeneration via TGF, BMP, Wnt, and FGF signaling pathways. Neural crest (NC) cells are multipotent, and once induced, will follow specific paths to migrate to different locations of the body where they give rise to a diverse array of cell types and tissues...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/29138054/keratinocyte-sonic-hedgehog-up-regulation-drives-the-development-of-giant-congenital-nevi-via-paracrine-endothelin-1-secretion
#14
Arash Chitsazan, Blake Ferguson, Rehan Villani, Herlina Y Handoko, Pamela Mukhopadhyay, Brian Gabrielli, Wolter J Mooi, H Peter Soyer, Duncan Lambie, Kiarash Khosrotehrani, Grant Morahan, Graeme J Walker
Giant congenital nevi are associated with clinical complications such as neurocutaneous melanosis and melanoma. Virtually nothing is known about why some individuals develop these lesions. We previously identified the sonic hedgehog (Shh) pathway regulator Cdon as a candidate nevus modifier gene. Here we validate this by studying Cdon knockout mice, and go on to establishment the mechanism by which Shh exacerbates nevogenesis. Cdon knockout mice develop blue nevi without the need for somatic melanocyte oncogenic mutation...
November 11, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29137928/camkii%C3%AE-expression-in-a-mouse-model-of-nmdar-hypofunction-schizophrenia-putative-roles-for-igf-1r-and-tlr4
#15
O M Ogundele, C C Lee
Schizophrenia (SCZ) is a neuropsychiatric disorder that is linked to social behavioral deficits and other negative symptoms associated with hippocampal synaptic dysfunction. Synaptic mechanism of schizophrenia is characterized by loss of hippocampal N-Methyl-d-Aspartate Receptor (NMDAR) activity (NMDAR hypofunction) and dendritic spines. Previous studies show that genetic deletion of hippocampal synaptic regulatory calcium-calmodulin dependent kinase II alpha (CaMKIIα) cause synaptic and behavioral defects associated with schizophrenia in mice...
November 11, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/29137234/the-af4-mll-fusion-transiently-augments-multilineage-hematopoietic-engraftment-but-is-not-sufficient-to-initiate-leukemia-in-cord-blood-cd34-cells
#16
Cristina Prieto, Rolf Marschalek, Alessa Kühn, Adelheid Bursen, Clara Bueno, Pablo Menéndez
The translocation t(4;11)(q21;q23) is the hallmark genetic abnormality associated with infant pro-B acute lymphoblastic leukemia (B-ALL) and has the highest frequency of rearrangement in Mixed-lineage leukemia (MLL) leukemias. Unlike other MLL translocations, MLL-AF4-induced proB-ALL is exceptionally difficult to model in mice/humans. Previous work has investigated the relevance of the reciprocal translocation fusion protein AF4-MLL for t(4;11) leukemia, finding that AF4-MLL is capable of inducing proB-ALL without requirement for MLL-AF4 when expressed in murine hematopoietic stem/progenitor cells (HSPCs)...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137224/role-of-the-inflammasome-in-chronic-obstructive-pulmonary-disease-copd
#17
Chiara Colarusso, Michela Terlizzi, Antonio Molino, Aldo Pinto, Rosalinda Sorrentino
Inflammation is central to the development of chronic obstructive pulmonary disease (COPD), a pulmonary disorder characterized by chronic bronchitis, chronic airway obstruction, emphysema, associated to progressive and irreversible decline of lung function. Emerging genetic and pharmacological evidence suggests that IL-1-like cytokines are highly detected in the sputum and broncho-alveolar lavage (BAL) of COPD patients, implying the involvement of the multiprotein complex inflammasome. So far, scientific evidence has focused on nucleotide-binding oligomerization domain-like receptors protein 3 (NLRP3) inflammasome, a specialized inflammatory signaling platform that governs the maturation and secretion of IL-1-like cytokines through the regulation of caspase-1-dependent proteolytic processing...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136505/inhibition-of-trf1-telomere-protein-impairs-tumor-initiation-and-progression-in-glioblastoma-mouse-models-and-patient-derived-xenografts
#18
Leire Bejarano, Alberto J Schuhmacher, Marinela Méndez, Diego Megías, Carmen Blanco-Aparicio, Sonia Martínez, Joaquín Pastor, Massimo Squatrito, Maria A Blasco
Glioblastoma multiforme (GBM) is a deadly and common brain tumor. Poor prognosis is linked to high proliferation and cell heterogeneity, including glioma stem cells (GSCs). Telomere genes are frequently mutated. The telomere binding protein TRF1 is essential for telomere protection, and for adult and pluripotent stem cells. Here, we find TRF1 upregulation in mouse and human GBM. Brain-specific Trf1 genetic deletion in GBM mouse models inhibited GBM initiation and progression, increasing survival. Trf1 deletion increased telomeric DNA damage and reduced proliferation and stemness...
November 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29136322/heme-oxygenase-1-regulates-sirtuin-1-autophagy-pathway-in-liver-transplantation-from-mouse-to-human
#19
Kojiro Nakamura, Shoichi Kageyama, Shi Yue, Jing Huang, Takehiro Fujii, Bibo Ke, Rebecca A Sosa, Elaine F Reed, Nakul Datta, Ali Zarrinpar, Ronald W Busuttil, Jerzy W Kupiec-Weglinski
Liver ischemia-reperfusion injury (IRI) represents a major risk factor of early graft dysfunction and a key obstacle to expanding the donor pool in orthotopic liver transplantation (OLT). Although graft autophagy is essential for resistance against hepatic IRI, its significance in clinical OLT remains unknown. Despite recent data identifying heme oxygenase-1 (HO-1) as a putative autophagy inducer, its role in OLT and interactions with Sirtuin-1 (SIRT1), a key autophagy regulator, have not been studied. We aimed to examine HO-1 mediated autophagy induction in human OLT and in a murine OLT model with extended (20h) cold storage, as well as to analyze the requirement for SIRT1 in autophagy regulation by HO-1...
November 14, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29136208/mouse-phenome-database-an-integrative-database-and-analysis-suite-for-curated-empirical-phenotype-data-from-laboratory-mice
#20
Molly A Bogue, Stephen C Grubb, David O Walton, Vivek M Philip, Georgi Kolishovski, Tim Stearns, Matthew H Dunn, Daniel A Skelly, Beena Kadakkuzha, Gregg TeHennepe, Govindarajan Kunde-Ramamoorthy, Elissa J Chesler
The Mouse Phenome Database (MPD; https://phenome.jax.org) is a widely used resource that provides access to primary experimental trait data, genotypic variation, protocols and analysis tools for mouse genetic studies. Data are contributed by investigators worldwide and represent a broad scope of phenotyping endpoints and disease-related traits in naïve mice and those exposed to drugs, environmental agents or other treatments. MPD houses individual animal data with detailed, searchable protocols, and makes these data available to other resources via API...
November 10, 2017: Nucleic Acids Research
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