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https://www.readbyqxmd.com/read/28231307/differential-regulation-of-c5a-receptor-1-in-innate-immune-cells-during-the-allergic-asthma-effector-phase
#1
Fanny Ender, Anna V Wiese, Inken Schmudde, Jing Sun, Tillman Vollbrandt, Peter König, Yves Laumonnier, Jörg Köhl
C5a drives airway constriction and inflammation during the effector phase of allergic asthma, mainly through the activation of C5a receptor 1 (C5aR1). Yet, C5aR1 expression on myeloid and lymphoid cells during the allergic effector phase is ill-defined. Recently, we generated and characterized a floxed green fluorescent protein (GFP)-C5aR1 knock-in mouse. Here, we used this reporter strain to monitor C5aR1 expression in airway, pulmonary and lymph node cells during the effector phase of OVA-driven allergic asthma...
2017: PloS One
https://www.readbyqxmd.com/read/28230213/knock-in-human-fgfr3-achondroplasia-mutation-as-a-mouse-model-for-human-skeletal-dysplasia
#2
Yi-Ching Lee, I-Wen Song, Ya-Ju Pai, Sheng-De Chen, Yuan-Tsong Chen
Achondroplasia (ACH), the most common genetic dwarfism in human, is caused by a gain-of function mutation in fibroblast growth factor receptor 3 (FGFR3). Currently, there is no effective treatment for ACH. The development of an appropriate human-relevant model is important for testing potential therapeutic interventions before human clinical trials. Here, we have generated an ACH mouse model in which the endogenous mouse Fgfr3 gene was replaced with human FGFR3(G380R) (FGFR3(ACH)) cDNA, the most common mutation in human ACH...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28223918/rpph1-upregulates-cdc42-expression-and-promotes-hippocampal-neuron-dendritic-spine-formation-by-competing-with-mir-330-5p
#3
Yifei Cai, Ziling Sun, Huizhen Jia, Hongxue Luo, Xiaoyang Ye, Qi Wu, Yi Xiong, Wei Zhang, Jun Wan
Alzheimer's disease (AD) is a heterogeneous neurodegenerative disease. Recent studies employing microRNA-seq and genome-wide sequencing have identified some non-coding RNAs that are influentially involved in AD pathogenesis. Non-coding RNAs can compete with other endogenous RNAs by microRNA response elements (MREs) and manipulate biological processes, such as tumorigenesis. However, only a few non-coding RNAs have been reported in the pathogenesis of AD. In this study, we constructed the first competing endogenous RNA (ceRNA) network leveraging whole transcriptome sequencing and a previously studied microRNA-seq of APPswe/PS1ΔE9 transgenic mice...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28222506/synaptic-compensation-as-a-probable-cause-of-prolonged-mild-cognitive-impairment-in-alzheimer-s-disease-implications-from-a-transgenic-mouse-model-of-the-disease
#4
Narjes Baazaoui, Michael Flory, Khalid Iqbal
Alzheimer's disease (AD) is a slow, progressive neurodegenerative disease in which cognitive decline takes place over a period of several years with a very variable period of mild cognitive impairment (MCI) and, in some cases, relatively long period before progression to dementia. The cognitive deficit during MCI is probably due to neuronal loss, an intermediate level of amyloid-β (Aβ) plaques and neurofibrillary tangles (NFT) and synaptosis, which is interrupted with a transient compensatory increase. We found impairment in reference memory accompanied by a decrease in the expression of synaptophysin, β-III tubulin, and MAP2 and a trend for GluR1, at 12 weeks of age in 3xTg-AD mice (hAPPSwe, P301L tau, PS1 [M146V] knock-in), a widely used transgenic model of AD...
February 7, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28219898/sk4-k-channels-are-therapeutic-targets-for-the-treatment-of-cardiac-arrhythmias
#5
Shiraz Haron-Khun, David Weisbrod, Hanna Bueno, Dor Yadin, Joachim Behar, Asher Peretz, Ofer Binah, Edith Hochhauser, Michael Eldar, Yael Yaniv, Michael Arad, Bernard Attali
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a stress-provoked ventricular arrhythmia, which also manifests sinoatrial node (SAN) dysfunction. We recently showed that SK4 calcium-activated potassium channels are important for automaticity of cardiomyocytes derived from human embryonic stem cells. Here SK4 channels were identified in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from healthy and CPVT2 patients bearing a mutation in calsequestrin 2 (CASQ2-D307H) and in SAN cells from WT and CASQ2-D307H knock-in (KI) mice...
February 20, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28216386/serotonin-disturbs-colon-epithelial-tolerance-of-commensal-e-coli-by-increasing-nox-2-derived-superoxide
#6
Suhrid Banskota, Sushil Chandra Regmi, Jaya Gautam, Pallavi Gurung, Yu-Jeong Lee, Sae Kwang Ku, Jin-Hyung Lee, Jintae Lee, Hyeun Wook Chang, Sang Joon Park, Jung-Ae Kim
Adherent-invasive E. coli colonization and Toll-like receptor (TLR) expression are increased in the gut of inflammatory bowel disease (IBD) patients. However, the underlying mechanism of such changes has not been determined. In the current study, it was examined whether gut serotonin (5-hydroxytryptamine, 5-HT) can induce adherent-invasive E. coli colonization and increase TLR expression. In a co-culture system, commensal E. coli strain (BW25113, BW) adhered minimally to colon epithelial cells, but this was significantly enhanced by 5-HT to the level of a pathogenic strain (EDL933)...
February 16, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28215987/accelerated-retinal-aging-in-pacap-knock-out-mice
#7
Andrea Kovács-Valasek, Krisztina Szabadfi, Viktória Dénes, Bálint Szalontai, Andrea Tamás, Péter Kiss, Aliz Szabó, Gyorgy Setalo, Dóra Reglődi, Robert Gábriel
Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurotrophic and neuroprotective peptide. PACAP and its receptors are widely distributed in the retina. A number of reports provided evidence that PACAP is neuroprotective in retinal degenerations. The current study compared retina cell type-specific differences in young (3-4months) and aged adults (14-16months), of wild-type (WT) mice and knock-out (KO) mice lacking endogenous PACAP production during the course of aging. Histological, immunocytochemical and Western blot examinations were performed...
February 13, 2017: Neuroscience
https://www.readbyqxmd.com/read/28213819/conditional-knockout-of-activin-like-kinase-1-alk-1-leads-to-heart-failure-without-maladaptive-remodeling
#8
Kevin J Morine, Xiaoying Qiao, Vikram Paruchuri, Mark J Aronovitz, Emily E Mackey, Lyanne Buiten, Jonathan Levine, Keshan Ughreja, Prerna Nepali, Robert M Blanton, Richard H Karas, S Paul Oh, Navin K Kapur
Activin like kinase-1 (AlK-1) mediates signaling via the transforming growth factor beta (TGFβ) family of ligands. AlK-1 activity promotes endothelial proliferation and migration. Reduced AlK-1 activity is associated with arteriovenous malformations. No studies have examined the effect of global AlK-1 deletion on indices of cardiac remodeling. We hypothesized that reduced levels of AlK-1 promote maladaptive cardiac remodeling. To test this hypothesis, we employed AlK-1 conditional knockout mice (cKO) harboring the ROSA26-CreER knock-in allele, whereby a single dose of intraperitoneal tamoxifen triggered ubiquitous Cre recombinase-mediated excision of floxed AlK-1 alleles...
February 17, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28213473/central-role-of-t-helper-17-cells-in-chronic-hypoxia-induced-pulmonary-hypertension
#9
Levi D Maston, David T Jones, Wieslawa Giermakowska, Tamara A Howard, Judy L Cannon, Wei Wang, Yongyi Wei, Weimin Xuan, Thomas C Resta, Laura V Gonzalez Bosc
RATIONALE: Inflammation is a prominent pathologic feature in pulmonary arterial hypertension as demonstrated by pulmonary vascular infiltration of inflammatory cells, including T and B lymphocytes. However, the contribution of the adaptive immune system is not well characterized in pulmonary hypertension caused by chronic hypoxia. CD4(+) T cells are required for initiating and maintaining inflammation, suggesting these cells could play an important role in the pathogenesis of hypoxic pulmonary hypertension...
February 17, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28213441/secreted-metalloproteinase-adamts-3-inactivates-reelin
#10
Himari Ogino, Arisa Hisanaga, Takao Kohno, Yuta Kondo, Kyoko Okumura, Takana Kamei, Tempei Sato, Hiroshi Asahara, Hitomi Tsuiji, Masaki Fukata, Mitsuharu Hattori
The secreted glycoprotein Reelin regulates embryonic brain development and adult brain functions. It has been suggested that reduced Reelin activity contributes to the pathogenesis of several neuropsychiatric and neurodegenerative disorders, such as schizophrenia and Alzheimer's disease; however, non-invasive methods that can upregulate Reelin activity in vivo have yet to be developed. We previously found that the proteolytic cleavage of Reelin within Reelin repeat 3 (N-t site) abolishes Reelin activity in vitro, but it remains controversial as to whether this effect occurs in vivo Here we partially purified the enzyme that mediates the N-t cleavage of Reelin from the culture supernatant of cerebral cortical neurons...
February 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28213154/density-and-neurochemical-profiles-of-neuronal-nitric-oxide-synthase-expressing-interneuron-in-the-mouse-basolateral-amygdala
#11
Xiaona Wang, Chunhua Liu, Xiaochen Wang, Fei Gao, Ren-Zhi Zhan
Neuronal nitric oxide synthase (nNOS)-expressing interneurons reside in the basolateral nucleus of the amygdala (BLA) of rodents. In the present study, we immunohistochemically analyzed nNOS-positive cells in the mouse BLA by focusing on their density, γ-Aminobutyric acid (GABA)ergicity, and co-localization with calcium-binding proteins and neuropeptides. The density of nNOS-containing neurons was analyzed with unbiased stereology. Experiments were conducted in both adult wild-type C57BL/6 and glutamic acid decarboxylase-green fluorescence protein (GAD67-GFP) knock-in mice, in which GFP is expressed in GABAergic neurons under the control of the endogenous GAD67 gene promoter...
February 14, 2017: Brain Research
https://www.readbyqxmd.com/read/28211815/generation-and-characterization-of-knock-in-mouse-models-expressing-versions-of-huntingtin-with-either-an-n17-or-a-combined-polyq-and-proline-rich-region-deletion
#12
Emily A André, Elise M Braatz, Jeh-Ping Liu, Scott O Zeitlin
BACKGROUND: The polyglutamine (polyQ) stretch of the Huntingtin protein (HTT) in mammals is flanked by a highly conserved 17 amino acid N-terminal domain (N17), and a proline-rich region (PRR). The PRR is a binding site for many HTT-interacting proteins, and the N17 domain regulates several normal HTT functions, including HTT's ability to associate with membranes and organelles. OBJECTIVE: This study investigates the consequence of deleting mouse Huntingtin's (Htt's) N17 domain or a combination of its polyQ stretch and PRR (QP) on normal Htt function in mice...
February 16, 2017: Journal of Huntington's Disease
https://www.readbyqxmd.com/read/28209967/optimization-of-the-production-of-knock-in-alleles-by-crispr-cas9-microinjection-into-the-mouse-zygote
#13
Aurélien Raveux, Sandrine Vandormael-Pournin, Michel Cohen-Tannoudji
Microinjection of the CRISPR/Cas9 system in zygotes is an efficient and comparatively fast method to generate genetically modified mice. So far, only few knock-in mice have been generated using this approach, and because no systematic study has been performed, parameters controlling the efficacy of CRISPR/Cas9-mediated targeted insertion are not fully established. Here, we evaluated the effect of several parameters on knock-in efficiency changing only one variable at a time. We found that knock-in efficiency was dependent on injected Cas9 mRNA and single-guide RNA concentrations and that cytoplasmic injection resulted in more genotypic complexity compared to pronuclear injection...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209720/acquired-expression-of-cbl-q367p-in-mice-induces-dysplastic-myelopoiesis-mimicking-chronic-myelomonocytic-leukemia
#14
Yuichiro Nakata, Takeshi Ueda, Akiko Nagamachi, Norimasa Yamasaki, Ken-Ichiro Ikeda, Yasuyuki Sera, Keiyo Takubo, Akinori Kanai, Hideaki Oda, Masashi Sanada, Seishi Ogawa, Kohichiro Tsuji, Yasuhiro Ebihara, Linda Wolff, Zen-Ichiro Honda, Toshio Suda, Toshiya Inaba, Hiroaki Honda
Chronic myelomonocytic leukemia (CMML) is a hematological malignancy characterized by uncontrolled proliferation of dysplastic myelomonocytes and frequent progression to acute myeloid leukemia (AML). We identified mutations in the Cbl gene, which encodes a negative regulator of cytokine signaling, in a subset of CMML patients. To investigate the contribution of mutant Cbl in CMML pathogenesis, we generated conditional knock-in mice for Cbl that express wild-type Cbl in a steady state and inducibly express Cbl(Q367P) , a CMML-associated Cbl mutant...
February 16, 2017: Blood
https://www.readbyqxmd.com/read/28209530/slc39a6-promotes-aggressiveness-of-esophageal-carcinoma-cells-by-increasing-intracellular-levels-of-zinc-activating-phosphatidylinositol-3-kinase-signaling-and-upregulating-genes-that-regulate-metastasis
#15
Xinxin Cheng, Lixuan Wei, Xudong Huang, Jian Zheng, Mingming Shao, Ting Feng, Jun Li, Yaling Han, Wenle Tan, Wen Tan, Dongxin Lin, Chen Wu
BACKGROUND & AIMS: A common variant in the solute carrier family 39 member 6 gene (SLC39A6) has been associated with survival times of patients with esophageal squamous-cell carcinoma (ESCC). We investigated the function of SLC39A6 and ways in which this variant affects tumor progression by studying ESCC samples and cell lines. METHODS: SLC39A6 was expressed, or knocked down by expression of small hairpin RNAs, in ESCC cells (KYSE30 and KYSE450) and HeLa cells using lentiviral vectors; we analyzed effects on proliferation, colony formation, migration, and invasion in vitro...
February 13, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28207852/tetraspanin-6-a-novel-regulator-of-hippocampal-synaptic-transmission-and-long-term-plasticity
#16
Isabel H Salas, Zsuzsanna Callaerts-Vegh, Amaia M Arranz, Francesc X Guix, Rudi D'Hooge, José A Esteban, Bart De Strooper, Carlos G Dotti
Tetraspanins (Tspan) are transmembrane proteins with important scaffold and signalling functions. Deletions of Tetraspanin 6 (Tspan6) gene, a member of the tetraspanin family, have been reported in patients with Epilepsy Female-restricted with Mental Retardation (EFMR). Interestingly, mutations in Tspan7, highly homologous to Tspan6, are associated with X-linked intellectual disability, suggesting that these two proteins are important for cognition. Considering recent evidences showing that Tspan7 plays a key role in synapse development and AMPAR trafficking, we initiated the study of Tspan6 in synaptic function using a Tspan6 knock out mouse model...
2017: PloS One
https://www.readbyqxmd.com/read/28206686/nte-pnpla6-is-expressed-in-mature-schwann-cells-and-is-required-for-glial-ensheathment-of-remak-fibers
#17
Janis McFerrin, Bruce L Patton, Elizabeth R Sunderhaus, Doris Kretzschmar
Neuropathy target esterase (NTE) or patatin-like phospholipase domain containing 6 (PNPLA6) was first linked with a neuropathy occurring after organophosphate poisoning and was later also found to cause complex syndromes when mutated, which can include mental retardation, spastic paraplegia, ataxia, and blindness. NTE/PNPLA6 is widely expressed in neurons but experiments with its Drosophila orthologue Swiss-cheese (SWS) suggested that it may also have glial functions. Investigating whether NTE/PNPLA6 is expressed in glia, we found that NTE/PNPLA6 is expressed by Schwann cells in the sciatic nerve of adult mice with the most prominent expression in nonmyelinating Schwann cells...
February 16, 2017: Glia
https://www.readbyqxmd.com/read/28202908/silencing-c-rel-in-macrophages-dampens-th1-and-th17-immune-responses-and-alleviates-experimental-autoimmune-encephalomyelitis-in-mice
#18
Hongling Zhang, Jiacheng Bi, Huqiang Yi, Tingting Fan, Qingguo Ruan, Lintao Cai, Youhai H Chen, Xiaochun Wan
Autoimmune Th1 and Th17 responses are critical for the development of central nervous system (CNS) pathology in experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis. Although macrophages play important roles in the development of Th1 and Th17 responses, whether modulating macrophage gene transcription can diminish Th1- and Th17 cell-induced CNS pathology is unclear. In this study, we successfully silenced the expression of the transcription factor c-Rel in macrophages of mice with EAE (including those infiltrating the CNS) using chemically modified c-Rel-specific siRNAs delivered by nanoparticles...
February 16, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28202907/calpain-1-deletion-impairs-mglur-dependent-ltd-and-fear-memory-extinction
#19
Guoqi Zhu, Victor Briz, Jeff Seinfeld, Yan Liu, Xiaoning Bi, Michel Baudry
Recent studies indicate that calpain-1 is required for the induction of long-term potentiation (LTP) elicited by theta-burst stimulation in field CA1 of hippocampus. Here we determined the contribution of calpain-1 in another type of synaptic plasticity, the long-term depression (LTD) elicited by activation of type-I metabotropic glutamate receptors (mGluR-LTD). mGluR-LTD was associated with calpain-1 activation following T-type calcium channel opening, and resulted in the truncation of a regulatory subunit of PP2A, B56α...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202618/the-inflammatory-bowel-disease-associated-autophagy-gene-atg16l1t300a-acts-as-a-dominant-negative-variant-in-mice
#20
Ping Gao, Hongtao Liu, Huarong Huang, Qi Zhang, Warren Strober, Fuping Zhang
The basis of the increased risk for Crohn's disease conferred by the Atg16L1T300A polymorphism is incompletely understood. An important step forward came from the recent demonstration that the murine equivalent of Atg16L1T300A (Atg16L1T316A) exhibits increased susceptibility to caspase 3-mediated cleavage and resulting decreased levels of full-length Atg16L1 in macrophages. However, although this finding showed that this polymorphism is a loss-of-function abnormality, it did not address the possibility that this polymorphism also affects the function of a normal Atg16L1 allele in heterozygous mice...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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