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https://www.readbyqxmd.com/read/28533224/microrna-196b-5p-regulates-colorectal-cancer-cell-migration-and-metastases-through-interaction-of-hoxb7-and-galnt5
#1
Verena Stiegelbauer, Petra Vychytilova-Faltejskova, Michael Karbiener, Anna-Maria Pehserl, Andreas Reicher, Margit Resel, Ellen Heitzer, Cristina Ivan, Marc D Bullock, Hui Ling, Alexander Ja Deutsch, Annika Wulf-Goldenberg, Jan Basri Adiprasito, Herbert Stöger, Johannes Haybaeck, Marek Svoboda, Michael Stotz, Gerald Höfler, Ondrej Slaby, George A Calin, Armin Gerger, Martin Pichler
Purpose: MicroRNA-196b-5p (miR-196b-5p) has been previously implicated in malignant transformation, however, its role in colorectal cancer (CRC) has not been fully explored. In the current study, we examine the clinical and biological relevance of miR-196b-5p, and the molecular pathways regulated by miR-196b-5p in CRC. <p>Experimental design: MiR-196b-5p expression was quantitated by qRT-PCR in two independent cohorts comprised of 292 CRC patients in total, to explore its biomarker potential. Transient and stable gain and loss of function experiments were conducted in a panel of CRC cell lines and mice, to evaluate the impact of miR-196b-5p on proliferation, chemo-sensitivity, migration/invasion and metastases formation in vitro and in vivo The molecular pathways influenced by miR-196b-5p were characterized using whole transcriptome profiling, in-silico target prediction tools, luciferase-interaction assays, and pheno-copy/rescue gene knock-down experiments...
May 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28533191/mir-34a-knockout-attenuates-cognitive-deficits-in-app-ps1-mice-through-inhibition-of-the-amyloidogenic-processing-of-app
#2
Chongdong Jian, Mengru Lu, Zhao Zhang, Long Liu, Xianfeng Li, Fang Huang, Ning Xu, Lina Qin, Qian Zhang, Donghua Zou
The noncoding miRNA-34a (miR-34a) is involved in Alzheimer's disease (AD) pathologenesis and shows potential for application as a biomarker for early diagnosis and intervention. Here, we established miR-34a knockout mice in an APP/PS1 background (APP/PS1-miR-34a KO mice) by crossbreeding miR-34a(-/-) mice with APP/PS1 mice. We then investigated cognitive impairment and related pathologies. The results showed that the level of miR-34a was increased at about 6months in APP/PS1 mice, consistent with the increase in amyloid β (Aβ), and cognitive function was significantly improved in mice when miR-34a was knocked out in 9-month-old and 12-month-old mice, indicating that miR-34a is a potential candidate for determining the progression of AD...
May 19, 2017: Life Sciences
https://www.readbyqxmd.com/read/28532818/tdp-43-upregulation-mediated-by-the-nlrp3-inflammasome-induces-cognitive-impairment-in-2-2-4-4-tetrabromodiphenyl-ether-bde-47-treated-mice
#3
Juan Zhuang, Xin Wen, Yan-Qiu Zhang, Qun Shan, Zi-Feng Zhang, Gui-Hong Zheng, Shao-Hua Fan, Meng-Qiu Li, Dong-Mei Wu, Bin Hu, Jun Lu, Yuan-Lin Zheng
It is now commonly known that exposure to polybrominated diphenyl ethers (PBDEs) may cause neurotoxicity and cognitive deficits in children as well as adults, but the underlying mechanisms are still not clear. In the present study, we aimed to elucidate the potential underlying mechanism of 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47)-induced neurotoxicity and cognitive impairment. Our results showed that BDE-47-treated mice exhibited impaired cognition and robust upregulation of nuclear TDP-43 in the hippocampus...
May 19, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28532411/aldehyde-dehydrogenase-2-2-knock-in-mice-show-increased-reactive-oxygen-species-production-in-response-to-cisplatin-treatment
#4
Jeewon Kim, Che-Hong Chen, Jieying Yang, Daria Mochly-Rosen
BACKGROUND: The aldehyde dehydrogenase (ALDH) enzyme family metabolizes and detoxifies both exogenous and endogenous aldehydes. Since chemotherapeutic agents, such as cisplatin, generate cytotoxic aldehydes and oxidative stress, and chemoresistant cancer cells express high levels of ALDH enzymes, we hypothesized that different ALDH expression within cells may show different chemosensitivity. ALDH2 has the lowest Km for acetaldehyde among ALDH isozymes and detoxifies acetaldehydes in addition to other reactive aldehydes, such as 4-hydroxy-nonenal, malondialdehyde and acrolein produced from lipid peroxidation by reactive oxygen species (ROS)...
May 22, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28524857/a-defined-metabolic-state-in-pre-b-cells-governs-b-cell-development-and-is-counterbalanced-by-swiprosin-2-efhd1
#5
Merle Stein, Sebastian Dütting, Dimitrios Mougiakakos, Michael Bösl, Kristin Fritsch, Dorothea Reimer, Sophia Urbanczyk, Tobit Steinmetz, Wolfgang Schuh, Aline Bozec, Thomas H Winkler, Hans-Martin Jäck, Dirk Mielenz
B-cell development in the bone marrow comprises proliferative and resting phases in different niches. We asked whether B-cell metabolism relates to these changes. Compared to pro B and small pre B cells, large pre B cells revealed the highest glucose uptake and ROS but not mitochondrial mass, whereas small pre B cells exhibited the lowest mitochondrial membrane potential. Small pre B cells from Rag1(-/-);33.C9 μ heavy chain knock-in mice revealed decreased glycolysis (ECAR) and mitochondrial spare capacity compared to pro B cells from Rag1(-/-) mice...
May 19, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28521463/endoplasmic-reticulum-protein-erp46-in-prostate-adenocarcinoma
#6
Wilhelmina C M Duivenvoorden, Sarah N Hopmans, Richard C Austin, Jehonathan H Pinthus
Endoplasmic reticulum (ER) protein ERp46 is a member of the protein disulfide isomerase family of oxidoreductases, which facilitates the reduction of disulfides in proteins and their folding. Accumulation of misfolded proteins has been implicated in cancer. The objectives of the present study were to investigate the role of ERp46 in prostate cancer, its expression and its effects on prostate cancer growth. A tissue microarray with human prostate cancer and normal prostate tissue samples was stained for ERp46 followed by image analysis...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28520872/glucocerebrosidase-deficiency-in-dopaminergic-neurons-induces-microglial-activation-without-neurodegeneration
#7
Federico N Soria, Michel Engeln, Marta Martinez-Vicente, Christelle Glangetas, María José López-González, Sandra Dovero, Benjamin Dehay, Elisabeth Normand, Miquel Vila, Alexandre Favereaux, François Georges, Christophe Lo Bianco, Erwan Bezard, Pierre-Olivier Fernagut
Mutations in the GBA1 gene encoding the lysosomal enzyme glucocerebrosidase (GBA1) are important risk factors for Parkinson's disease (PD). In vitro, altered GBA1 activity promotes alpha-synuclein accumulation while elevated levels of alpha-synuclein compromise GBA1 function, thus supporting a pathogenic mechanism in PD. However, the mechanisms by which GBA1 deficiency is linked to increased risk of PD remains elusive, partially because of lack of aged models of GBA1 deficiency. Since knocking-out GBA1 in the entire brain induces massive neurodegeneration and early death, we generated a mouse model of GBA1 deficiency amenable to investigate the long-term consequences of compromised GBA1 function in dopaminergic neurons...
May 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28520792/myd88-signaling-in-dendritic-cells-and-the-intestinal-epithelium-controls-immunity-against-intestinal-infection-with-c-rodentium
#8
Christin Friedrich, Panagiota Mamareli, Sophie Thiemann, Friederike Kruse, Zuobai Wang, Bernhard Holzmann, Till Strowig, Tim Sparwasser, Matthias Lochner
MyD88-mediated signaling downstream of Toll-like receptors and the IL-1 receptor family is critically involved in the induction of protective host responses upon infections. Although it is known that MyD88-deficient mice are highly susceptible to a wide range of bacterial infections, the cell type-specific contribution of MyD88 in protecting the host against intestinal bacterial infection is only poorly understood. In order to investigate the importance of MyD88 in specific immune and nonimmune cell types during intestinal infection, we employed a novel murine knock-in model for MyD88 that enables the cell type-specific reactivation of functional MyD88 expression in otherwise MyD88-deficient mice...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28520213/the-pnpla3-variant-associated-with-fatty-liver-disease-i148m-accumulates-on-lipid-droplets-by-evading-ubiquitylation
#9
Soumik BasuRay, Eriks Smagris, Jonathan C Cohen, Helen H Hobbs
A sequence variation (I148M) in patatin-like phospholipase domain-containing protein 3 (PNPLA3) is strongly associated with fatty liver disease (FLD), but the underlying mechanism remains obscure. Here we used knock-in (KI) mice (Pnpla3(148M/M) ) to examine the mechanism responsible for accumulation of triglyceride (TG) and PNPLA3 in hepatic lipid droplets (LDs). No differences were found between Pnpla3(148M/M) and Pnpla3(+/+) mice in hepatic TG synthesis, utilization, or secretion. These results are consistent with TG accumulation in the Pnpla3(148M/M) mice being caused by impaired TG mobilization from LDs...
May 18, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28518215/the-tlr9-signaling-pathway-regulates-mr1-mediated-bacterial-antigen-presentation-in-b-cells
#10
Jianyun Liu, Randy R Brutkiewicz
Mucosal-associated invariant T (MAIT) cells are conserved T cells that express a semi-invariant TCR (Vα7.2 in humans and Vα19 in mice). The development of MAIT cells requires the antigen (Ag) presenting MHC-related protein 1 (MR1), as well as commensal bacteria. The mechanisms that regulate the functional expression of MR1 molecules and their loading with bacterial Ag in APCs are largely unknown. We have found that treating B cells with the TLR9 agonist CpG increases MR1 surface expression. Interestingly, activation of TLR9 by CpG-A (but not CpG-B) enhances MR1 surface expression...
May 18, 2017: Immunology
https://www.readbyqxmd.com/read/28518123/expression-of-exogenous-cytokine-in-patient-derived-xenografts-via-injection-with-a-cytokine-transduced-stromal-cell-line
#11
Jacqueline S Coats, Ineavely Baez, Cornelia Stoian, Terry-Ann M Milford, Xiaobing Zhang, Olivia L Francis, Ruijun Su, Kimberly J Payne
Patient-derived xenograft (PDX) mice are produced by transplanting human cells into immune deficient mice. These models are an important tool for studying the mechanisms of normal and malignant hematopoiesis and are the gold standard for identifying effective chemotherapies for many malignancies. PDX models are possible because many of the mouse cytokines also act on human cells. However, this is not the case for all cytokines, including many that are critical for studying normal and malignant hematopoiesis in human cells...
May 10, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28518103/structure-function-studies-in-mouse-embryonic-stem-cells-using-recombinase-mediated-cassette-exchange
#12
Tim Pieters, Lieven Haenebalcke, Kenneth Bruneel, Niels Vandamme, Tino Hochepied, Jolanda van Hengel, Dagmar Wirth, Geert Berx, Jody J Haigh, Frans van Roy, Steven Goossens
Gene engineering in mouse embryos or embryonic stem cells (mESCs) allows for the study of the function of a given protein. Proteins are the workhorses of the cell and often consist of multiple functional domains, which can be influenced by posttranslational modifications. The depletion of the entire protein in conditional or constitutive knock-out (KO) mice does not take into account this functional diversity and regulation. An mESC line and a derived mouse model, in which a docking site for FLPe recombination-mediated cassette exchange (RMCE) was inserted within the ROSA26 (R26) locus, was previously reported...
April 27, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28515850/dissection-of-z-disc-myopalladin-gene-network-involved-in-the-development-of-restrictive-cardiomyopathy-using-system-genetics-approach
#13
Qingqing Gu, Uzmee Mendsaikhan, Zaza Khuchua, Byron C Jones, Lu Lu, Jeffrey A Towbin, Biao Xu, Enkhsaikhan Purevjav
AIM: To investigate the regulation of Myopalladin (Mypn) and identify its gene network involved in restrictive cardiomyopathy (RCM). METHODS: Gene expression values were measured in the heart of a large family of BXD recombinant inbred (RI) mice derived from C57BL/6J and DBA/2J. The proteomics data were collected from Mypn knock-in and knock-out mice. Expression quantitative trait locus (eQTL) mapping methods and gene enrichment analysis were used to identify Mypn regulation, gene pathway and co-expression networks...
April 26, 2017: World Journal of Cardiology
https://www.readbyqxmd.com/read/28515074/immune-checkpoints-on-innate-lymphoid-cells
#14
Laura Chiossone, Eric Vivier
In this issue of JEM, Taylor et al. (https://doi.org/10.1084/jem.20161653) describe PD-1 as a critical negative regulator of group 2 innate lymphoid cells (ILC-2s). PD-1 intrinsically controls proliferation and cytokine production of both mouse and human ILC-2s. PD-1 signaling inhibits STAT5 phosphorylation and the removal of this brake by knocking down PD-1 expression or by using anti-PD-1 blocking antibodies, translated in vivo into better clearance of helminth worm infection in mice.
May 17, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28513320/crispr-cas9-based-pten-knock-out-and-sleeping-beauty-transposon-mediated-nras-knock-in-induces-hepatocellular-carcinoma-and-hepatic-lipid-accumulation-in-mice
#15
Mingming Gao, Dexi Liu
Both Pten and Nras are downstream mediators of receptor tyrosine kinase activation that plays important roles in controlling cell survival and proliferation. Here, we investigated whether and how Pten loss cross-talks with Nras activation in driving liver cancer development in mice. Somatic disruption of hepatic Pten and overexpression of Nras were achieved in out-bred immunocompetent CD-1 mice through a hydrodynamic delivery of plasmids carrying Sleeping Beauty transposon-based integration of Nras and the CRISPR/Cas9-mediated Pten knock-out system...
May 17, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28511841/a-method-for-isolating-cortical-interneurons-sharing-the-same-birthdays-for-gene-expression-studies
#16
Hui Xuan Ng, Ean Phing Lee, Brenton L Cavanagh, Joanne M Britto, Seong-Seng Tan
The two neuronal populations in the cortex, pyramidal neurons and interneurons, can be separated based on neurotransmitter identity, however, within this segregation a large degree of diversity exists. Investigations into the molecular diversity of neurons are impeded by the inability to isolate cell populations born at different times for gene expression analysis. Developing interneurons may be distinguished by the expression of Glutamic Acid Decarboxylase-67 (GAD67). Neuronal birthdating using nucleoside analogs is an effective means of identifying coetaneous interneurons...
May 13, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28507548/iron-and-hepcidin-independent-downregulation-of-the-iron-exporter-ferroportin-in-macrophages-during-salmonella-infection
#17
Alexandra Willemetz, Sean Beatty, Etienne Richer, Aude Rubio, Anne Auriac, Ruth J Milkereit, Olivier Thibaudeau, Sophie Vaulont, Danielle Malo, François Canonne-Hergaux
Retention of iron in tissue macrophages via upregulation of hepcidin (HAMP) and downregulation of the iron exporter ferroportin (FPN) is thought to participate in the establishment of anemia of inflammation after infection. However, an upregulation of FPN has been proposed to limit macrophages iron access to intracellular pathogens. Therefore, we studied the iron homeostasis and in particular the regulation of FPN after infection with Salmonella enterica serovar Typhimurium in mice presenting tissue macrophages with high iron (AcB61), basal iron (A/J and wild-type mice), or low iron (Hamp knock out, Hamp(-/-)) levels...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28507102/foxo3-pgc-1%C3%AE-signaling-axis-is-essential-for-cancer-stem-cell-properties-of-pancreatic-ductal-adenocarcinoma
#18
Motofumi Kumazoe, Mika Takai, Shun Hiroi, Chieri Takeuchi, Mai Kadomatsu, Takashi Nojiri, Hiroaki Onda, Jaehoon Bae, Yuhui Huang, Kanako Takamatsu, Shuya Yamashita, Kenji Kangawa, Hirofumi Tachibana
In 95% of patients with pancreatic ductal adenocarcinoma (PDAC), recurrence is observed following chemotherapy. Findings from several studies have indicated that cancer stem cells (CSCs) are resistant to anti-cancer agents and may be involved in cancer recurrence and metastasis. The CD44 protein is a major CSC marker, and CD44 also plays an indispensable role in the CSC properties in several cancers, including pancreatic cancer; however, no clinical approach exists to inhibit CD44 activity. Here, we have performed knockin/knock down experiments and we demonstrate that the forkhead box O3 (FOXO3)/liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK)/PPAR-γ co-activator-1β (PGC- 1β)/pyruvate dehydrogenase -A1 (PDHA1) pathway is essential for CD44 expression and CSC properties...
May 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28505229/oligodendrocyte-and-neuron-specific-nogo-a-restrict-dendritic-branching-and-spine-density-in-the-adult-mouse-motor-cortex
#19
Ajmal Zemmar, Chia-Chien Chen, Oliver Weinmann, Brigitt Kast, Flora Vajda, James Bozeman, Noel Isaad, Yi Zuo, Martin E Schwab
Nogo-A has been well described as a myelin-associated inhibitor of neurite outgrowth and functional neuroregeneration after central nervous system (CNS) injury. Recently, a new role of Nogo-A has been identified as a negative regulator of synaptic plasticity in the uninjured adult CNS. Nogo-A is present in neurons and oligodendrocytes. However, it is yet unclear which of these two pools regulate synaptic plasticity. To address this question we used newly generated mouse lines in which Nogo-A is specifically knocked out in (1) oligodendrocytes (oligoNogo-A KO) or (2) neurons (neuroNogo-A KO)...
May 15, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28504423/genetic-vulnerabilities-to-prenatal-alcohol-exposure-limb-defects-in-sonic-hedgehog-and-gli2-heterozygous-mice
#20
Eric W Fish, Laura B Murdaugh, Kathleen K Sulik, Kevin P Williams, Scott E Parnell
BACKGROUND: Genetic factors influence the physical and neurobehavioral manifestations of prenatal alcohol exposure (PAE). Animal models allow the investigation of specific genes that confer vulnerability to, or protection from, birth defects associated with fetal alcohol spectrum disorders (FASDs). The objective of the present experiments was to determine if genetic alterations in the Sonic Hedgehog (Shh) signaling pathways affect the vulnerability to PAE-induced skeletal defects involving the forelimbs and/or hindlimbs...
May 15, 2017: Birth Defects Res
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