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Transgenic Models of Behaviour

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https://www.readbyqxmd.com/read/28416454/e1a-is-an-exogenous-in-vivo-tumour-suppressor
#1
F J Cimas, J L Callejas-Valera, D C García-Olmo, J Hernández-Losa, P Melgar-Rojas, M J Ruiz-Hidalgo, R Pascual-Serra, M Ortega-Muelas, O Roche, P Marcos, E Garcia-Gil, D M Fernandez-Aroca, S Ramón Y Cajal, J S Gutkind, R Sanchez-Prieto
The E1a gene from adenovirus has become a major tool in cancer research. Since the discovery of E1a, it has been proposed to be an oncogene, becoming a key element in the model of cooperation between oncogenes. However, E1a's in vivo behaviour is consistent with a tumour suppressor gene, due to the block/delay observed in different xenograft models. To clarify this interesting controversy, we have evaluated the effect of the E1a 13s isoform from adenovirus 5 in vivo. Initially, a conventional xenograft approach was performed using previously unreported HCT116 and B16-F10 cells, showing a clear anti-tumour effect regardless of the mouse's immunological background (immunosuppressed/immunocompetent)...
April 14, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28405401/drosophila-enhancer-gal4-lines-show-ectopic-expression-during-development
#2
Sergio Casas-Tintó, Mercedes Arnés, Alberto Ferrús
In Drosophila melanogaster the most widely used technique to drive gene expression is the binary UAS/Gal4 system. We show here that a set of nervous system specific enhancers (elav, D42/Toll-6, OK6/RapGAP1) display ectopic activity in epithelial tissues during development, which is seldom considered in experimental studies. This ectopic activity is variable, unstable and influenced by the primary sequence of the enhancer and the insertion site in the chromosome. In addition, the ectopic activity is independent of the protein expressed, Gal4, as it is reproduced also with the expression of Gal80...
March 2017: Royal Society Open Science
https://www.readbyqxmd.com/read/28397990/germline-transformation-of-the-western-corn-rootworm-diabrotica-virgifera-virgifera
#3
F Chu, W Klobasa, P Wu, S Pinzi, N Grubbs, S Gorski, Y Cardoza, M D Lorenzen
The western corn rootworm (WCR), a major pest of maize, is notorious for rapidly adapting biochemically, behaviourally and developmentally to a variety of control methods. Despite much effort, the genetic basis of WCR adaptation remains a mystery. Since transformation-based applications such as transposon tagging and enhancer trapping have facilitated genetic dissection of model species such as Drosophila melanogaster, we developed a germline-transformation system for WCR in an effort to gain a greater understanding of the basic biology of this economically important insect...
April 11, 2017: Insect Molecular Biology
https://www.readbyqxmd.com/read/28389761/a-stop-signal-task-for-sheep-introduction-and-validation-of-a-direct-measure-for-the-stop-signal-reaction-time
#4
Franziska Knolle, Sebastian D McBride, James E Stewart, Rita P Goncalves, A Jennifer Morton
Huntington's disease (HD) patients show reduced flexibility in inhibiting an already-started response. This can be quantified by the stop-signal task. The aim of this study was to develop and validate a sheep version of the stop-signal task that would be suitable for monitoring the progression of cognitive decline in a transgenic sheep model of HD. Using a semi-automated operant system, sheep were trained to perform in a two-choice discrimination task. In 22% of the trials, a stop-signal was presented. Upon the stop-signal presentation, the sheep had to inhibit their already-started response...
April 7, 2017: Animal Cognition
https://www.readbyqxmd.com/read/28379300/combined-effects-of-scanning-ultrasound-and-a-tau-specific-single-chain-antibody-in-a-tau-transgenic-mouse-model
#5
Rebecca M Nisbet, Ann Van der Jeugd, Gerhard Leinenga, Harrison T Evans, Phillip W Janowicz, Jürgen Götz
Alzheimer's disease is characterized by the deposition of amyloid-β as extracellular plaques and hyperphosphorylated tau as intracellular neurofibrillary tangles. Tau pathology characterizes not only Alzheimer's disease, but also many other tauopathies, presenting tau as an attractive therapeutic target. Passive tau immunotherapy has been previously explored; however, because only a small fraction of peripherally delivered antibodies crosses the blood-brain barrier, enters the brain and engages with tau that forms intracellular aggregates, more efficient ways of antibody delivery and neuronal uptake are warranted...
March 4, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28376796/ahcoda-db-a-data-repository-with-web-based-mining-tools-for-the-analysis-of-automated-high-content-mouse-phenomics-data
#6
Bastijn Koopmans, August B Smit, Matthijs Verhage, Maarten Loos
BACKGROUND: Systematic, standardized and in-depth phenotyping and data analyses of rodent behaviour empowers gene-function studies, drug testing and therapy design. However, no data repositories are currently available for standardized quality control, data analysis and mining at the resolution of individual mice. DESCRIPTION: Here, we present AHCODA-DB, a public data repository with standardized quality control and exclusion criteria aimed to enhance robustness of data, enabled with web-based mining tools for the analysis of individually and group-wise collected mouse phenotypic data...
April 4, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28369393/selective-rescue-of-heightened-anxiety-but-not-gait-ataxia-in-a-premutation-90cgg-mouse-model-of-fragile-x-associated-tremor-ataxia-syndrome
#7
Hoanna Castro, Emre Kul, Ronald A M Buijsen, Lies-Anne W F M Severijnen, Rob Willemsen, Renate K Hukema, Oliver Stork, Mónica Santos
A CGG-repeat expansion in the premutation range in the Fragile X mental retardation 1 gene (FMR1) has been identified as the genetic cause of Fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset neurodegenerative disorder that manifests with action tremor, gait ataxia and cognitive impairments. In this study we used a bigenic mouse model, in which expression of a 90CGG premutation tract is activated in neural cells upon doxycycline (DOX) administration - P90CGG mouse model. We here demonstrate the behavioural manifestation of clinically relevant features of FXTAS patients and premutation carrier individuals in this inducible mouse model...
March 22, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28336338/knockdown-of-appl-mimics-transgenic-a%C3%AE-induced-neurodegenerative-phenotypes-in-drosophila
#8
Sandeep Kumar Singh, Saurabh Srivastav, Amarish Kumar Yadav, Saripella Srikrishna
A variety of Drosophila mutant lines have been established as potential disease-models to study various disease mechanisms including human neurodegenerative diseases like Alzheimer's disease (AD), Huntington's disease (HD) and Parkinson's disease (PD). The evolutionary conservation of APP (Amyloid Precursor Protein) and APPL (Amyloid Precursor Protein-Like) and the comparable detrimental effects caused by their metabolic products strongly implies the conservation of their normal physiological functions. In view of this milieu, a comparative analysis on the pattern of neurodegenerative phenotypes between Drosophila APPL-RNAi line and transgenic Drosophila line expressing eye tissue specific human Aβ (Amyloid beta) was undertaken...
March 20, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28211486/motor-phenotype-is-not-associated-with-vascular-dysfunction-in-symptomatic-huntington-s-disease-transgenic-r6-2-160-cag-mice
#9
A Di Pardo, A Carrizzo, A Damato, S Castaldo, E Amico, L Capocci, M Ambrosio, F Pompeo, C De Sanctis, C C Spinelli, A A Puca, P Remondelli, V Maglione, C Vecchione
Whereas Huntington's disease (HD) is unequivocally a neurological disorder, a critical mass of emerging studies highlights the occurrence of peripheral pathology like cardiovascular defects in both animal models and humans. The overt impairment in cardiac function is normally expected to be associated with peripheral vascular dysfunction, however whether this assumption is reasonable or not in HD is still unknown. In this study we functionally characterized the vascular system in R6/2 mouse model (line 160 CAG), which recapitulates several features of human pathology including cardiac disease...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28167839/new-murine-niemann-pick-type-c-models-bearing-a-pseudoexon-generating-mutation-recapitulate-the-main-neurobehavioural-and-molecular-features-of-the-disease
#10
Marta Gómez-Grau, Júlia Albaigès, Josefina Casas, Carme Auladell, Mara Dierssen, Lluïsa Vilageliu, Daniel Grinberg
Niemann-Pick disease type C (NPC) is a rare neurovisceral disease caused mainly by mutations in the NPC1 gene. This autosomal recessive lysosomal disorder is characterised by the defective lysosomal secretion of cholesterol and sphingolipids. No effective therapy exists for the disease. We previously described a deep intronic point mutation (c.1554-1009 G > A) in NPC1 that generated a pseudoexon, which could be corrected at the cellular level using antisense oligonucleotides. Here, we describe the generation of two mouse models bearing this mutation, one in homozygosity and the other in compound heterozygosity with the c...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28160413/accelerated-aging-exacerbates-a-pre-existing-pathology-in-a-tau-transgenic-mouse-model
#11
Liviu-Gabriel Bodea, Harrison Tudor Evans, Ann Van der Jeugd, Lars M Ittner, Fabien Delerue, Jillian Kril, Glenda Halliday, John Hodges, Mathew C Kiernan, Jürgen Götz
Age is a critical factor in the prevalence of tauopathies, including Alzheimer's disease. To observe how an aging phenotype interacts with and affects the pathological intracellular accumulation of hyperphosphorylated tau, the tauopathy mouse model pR5 (expressing P301L mutant human tau) was back-crossed more than ten times onto a senescence-accelerated SAMP8 background to establish the new strain, SApT. Unlike SAMP8 mice, pR5 mice are characterized by a robust tau pathology particularly in the amygdala and hippocampus...
April 2017: Aging Cell
https://www.readbyqxmd.com/read/28093491/early-microgliosis-precedes-neuronal-loss-and-behavioural-impairment-in-mice-with-a-frontotemporal-dementia-causing-chmp2b-mutation
#12
Emma L Clayton, Renzo Mancuso, Troels Tolstrup Nielsen, Sarah Mizielinska, Holly Holmes, Nicholas Powell, Frances Norona, Jytte Overgaard Larsen, Carmelo Milioto, Katherine M Wilson, Mark F Lythgoe, Sebastian Ourselin, Jörgen E Nielsen, Peter Johannsen, Ida Holm, John Collinge, A Frej, Peter L Oliver, Diego Gomez-Nicola, Adrian M Isaacs
Frontotemporal dementia (FTD)-causing mutations in the CHMP2B gene lead to the generation of mutant C-terminally truncated CHMP2B. We report that transgenic mice expressing endogenous levels of mutant CHMP2B developed late-onset brain volume loss associated with frank neuronal loss and FTD-like changes in social behaviour. These data are the first to show neurodegeneration in mice expressing mutant CHMP2B and indicate that our mouse model is able to recapitulate neurodegenerative changes observed in FTD. Neuroinflammation has been increasingly implicated in neurodegeneration, including FTD...
January 16, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28025093/varenicline-improves-motor-and-cognitive-deficits-and-decreases-depressive-like-behaviour-in-late-stage-yac128-mice
#13
Ailsa L McGregor, Gary D'Souza, Donghyo Kim, Malcolm D Tingle
OBJECTIVE: Studies in the post mortem human brain and in genetic mouse model suggest that dysfunctional cholinergic neurotransmission, through a loss of agonist rather than receptors may be a significant contributing factor to HD pathology. If correct, pharmacological replacement may therefore be a potential treatment strategy. We have investigated whether chronic administration of the selective nicotinic partial agonist varenicline improved motor, cognitive and affective symptoms in a transgenic mouse model of Huntington's disease...
December 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/28017852/anxiety-and-risk-assessment-related-traits-in-a-rat-model-of-spinocerebellar-ataxia-type-17
#14
Elisavet I Kyriakou, Giuseppe Manfré, Jesús A Spadaro, Huu Phuc Nguyen, Johanneke E Van der Harst, Judith R Homberg
Anxiety as a common feature of several neurodegenerative/polyglutamine diseases is an important aspect for the face validity of an animal model for Spinocerebellar Ataxia type 17 (SCA17). Risk assessment and anxiety-like traits were characterised in 3-6-9 months old rats of a transgenic model for SCA17 using the standard behavioural test elevated plus maze. In addition, c-Fos immunostainings in the basolateral amygdala evaluated neuronal activation in correlation to the behavioural responses. The most prominent behavioural effect was a higher level of risk assessment in the transgenic rats...
March 15, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28007908/topoisomerase-1-inhibitor-topotecan-delays-the-disease-progression-in-a-mouse-model-of-huntington-s-disease
#15
Shashi Shekhar, Naman Vatsa, Vipendra Kumar, Brijesh Kumar Singh, Imran Jamal, Ankit Sharma, Nihar Ranjan Jana
Huntington's disease (HD) is a dominantly inherited progressive neurodegenerative disorder caused by the accumulation of polyglutamine expanded mutant huntingtin as inclusion bodies primarily in the brain. After the discovery of the HD gene, considerable progress has been made in understanding the disease pathogenesis and multiple drug targets have been identified, even though currently there is no effective therapy. Here, we demonstrate that the treatment of topotecan, a brain-penetrating topoisomerase 1 inhibitor, to HD transgenic mouse considerably improved its motor behavioural abnormalities along with a significant extension of lifespan...
January 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/27995281/the-use-of-stable-and-unstable-green-fluorescent-proteins-for-studies-in-two-bacterial-models-agrobacterium-tumefaciens-and-xanthomonas-campestris-pv-campestris
#16
Pilar Sabuquillo, Adela Gea, Isabel M Matas, Cayo Ramos, Jaime Cubero
Fluorescent proteins have been used to track plant pathogens to understand their host interactions. To be useful, the transgenic pathogens must present similar behaviour than the wild-type isolates. Herein, a GFP marker was used to transform two plant pathogenic bacteria, Agrobacterium and Xanthomonas, to localize and track the bacteria during infection. The transgenic bacteria were evaluated to determine whether they showed the same fitness than the wild-type strains or whether the expression of the GFP protein interfered in the bacterial activity...
December 19, 2016: Archives of Microbiology
https://www.readbyqxmd.com/read/27919712/extracts-from-two-ubiquitous-mediterranean-plants-ameliorate-cellular-and-animal-models-of-neurodegenerative-proteinopathies
#17
Michelle Briffa, Stephanie Ghio, Johanna Neuner, Alison J Gauci, Rebecca Cacciottolo, Christelle Marchal, Mario Caruana, Christophe Cullin, Neville Vassallo, Ruben J Cauchi
A signature feature of age-related neurodegenerative proteinopathies is the misfolding and aggregation of proteins, typically amyloid-β (Aβ) in Alzheimer's disease (AD) and α-synuclein (α-syn) in Parkinson's disease (PD), into soluble oligomeric structures that are highly neurotoxic. Cellular and animal models that faithfully replicate the hallmark features of these disorders are being increasing exploited to identify disease-modifying compounds. Natural compounds have been identified as a useful source of bioactive molecules with promising neuroprotective capabilities...
December 2, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27919008/phenotype-analysis-of-male-transgenic-mice-overexpressing-mutant-igfbp-2-lacking-the-cardin-weintraub-sequence-motif-reduced-expression-of-synaptic-markers-and-myelin-basic-protein-in-the-brain-and-a-lower-degree-of-anxiety-like-behaviour
#18
N Schindler, J Mayer, S Saenger, U Gimsa, C Walz, J Brenmoehl, D Ohde, E Wirthgen, A Tuchscherer, V C Russo, M Frank, T Kirschstein, F Metzger, A Hoeflich
Brain growth and function are regulated by insulin-like growth factors I and II (IGF-I and IGF-II) but also by IGF-binding proteins (IGFBPs), including IGFBP-2. In addition to modulating IGF activities, IGFBP-2 interacts with a number of components of the extracellular matrix and cell membrane via a Cardin-Weintraub sequence or heparin binding domain (HBD1). The nature and the signalling elicited by these interactions are not fully understood. Here, we examined transgenic mice (H1d-hBP2) overexpressing a mutant human IGFBP-2 that lacks a specific heparin binding domain (HBD1) known as the Cardin-Weintraub sequence...
November 16, 2016: Growth Hormone & IGF Research
https://www.readbyqxmd.com/read/27914975/techniques-for-chronic-monitoring-of-brain-activity-in-freely-moving-sheep-using-wireless-eeg-recording
#19
N Perentos, A U Nicol, A Q Martins, J E Stewart, P Taylor, A J Morton
BACKGROUND: Large mammals with complex central nervous systems offer new possibilities for translational research into basic brain function. Techniques for monitoring brain activity in large mammals, however, are not as well developed as they are in rodents. NEW METHOD: We have developed a method for chronic monitoring of electroencephalographic (EEG) activity in unrestrained sheep. We describe the methods for behavioural training prior to implantation, surgical procedures for implantation, a protocol for reliable anaesthesia and recovery, methods for EEG data collection, as well as data pertaining to suitability and longevity of different types of electrodes...
November 30, 2016: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/27893779/rapid-recovery-of-visual-function-associated-with-blue-cone-ablation-in-zebrafish
#20
Gordon F Hagerman, Nicole C L Noel, Sylvia Y Cao, Michèle G DuVal, A Phillip Oel, W Ted Allison
Hurdles in the treatment of retinal degeneration include managing the functional rewiring of surviving photoreceptors and integration of any newly added cells into the remaining second-order retinal neurons. Zebrafish are the premier genetic model for such questions, and we present two new transgenic lines allowing us to contrast vision loss and recovery following conditional ablation of specific cone types: UV or blue cones. The ablation of each cone type proved to be thorough (killing 80% of cells in each intended cone class), specific, and cell-autonomous...
2016: PloS One
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