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Transgenic Models of Behaviour

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https://www.readbyqxmd.com/read/28093491/early-microgliosis-precedes-neuronal-loss-and-behavioural-impairment-in-mice-with-a-frontotemporal-dementia-causing-chmp2b-mutation
#1
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
#2
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
#3
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...
December 23, 2016: 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
#4
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...
December 22, 2016: 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
#5
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
#6
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
#7
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-longitudinal-eeg-recording
#8
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
#9
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
https://www.readbyqxmd.com/read/27826792/monocyte-behaviour-and-tissue-transglutaminase-expression-during-experimental-autoimmune-encephalomyelitis-in-transgenic-cx3cr1-gfp-gfp-mice
#10
Navina L Chrobok, Alexandre Jaouen, Keith K Fenrich, John G J M Bol, Micha M M Wilhelmus, Benjamin Drukarch, Franck Debarbieux, Anne-Marie van Dam
Leukocyte infiltration into the central nervous system (CNS) is a key pathological feature in multiple sclerosis (MS) and the MS animal model experimental autoimmune encephalomyelitis (EAE). Recently, preventing leukocyte influx into the CNS of MS patients is the main target of MS therapies and insight into cell behaviour in the circulation is needed for further elucidation of such therapies. In this study, we aimed at in vivo visualization of monocytes in a time-dependent manner during EAE. Using intravital two-photon microscopy (IVM), we imaged CX3CR1(gfp/gfp) mice during EAE, visualizing CX3CR1-GFP(+) monocytes and their dynamics in the spinal cord vasculature...
November 9, 2016: Amino Acids
https://www.readbyqxmd.com/read/27797819/bimodal-behaviour-of-interfollicular-epidermal-progenitors-regulated-by-hair-follicle-position-and-cycling
#11
Edwige Roy, Zoltan Neufeld, Luca Cerone, Ho Yi Wong, Samantha Hodgson, Jean Livet, Kiarash Khosrotehrani
Interfollicular epidermal (IFE) homeostasis is a major physiological process allowing maintenance of the skin barrier function. Despite progress in our understanding of stem cell populations in different hair follicle compartments, cellular mechanisms of IFE maintenance, in particular, whether a hierarchy of progenitors exists within this compartment, have remained controversial. We here used multicolour lineage tracing with Brainbow transgenic labels activated in the epidermis to track individual keratinocyte clones...
December 15, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27561680/vcp-recruitment-to-mitochondria-causes-mitophagy-impairment-and-neurodegeneration-in-models-of-huntington-s-disease
#12
Xing Guo, XiaoYan Sun, Di Hu, Ya-Juan Wang, Hisashi Fujioka, Rajan Vyas, Sudha Chakrapani, Amit Umesh Joshi, Yu Luo, Daria Mochly-Rosen, Xin Qi
Mutant Huntingtin (mtHtt) causes neurodegeneration in Huntington's disease (HD) by evoking defects in the mitochondria, but the underlying mechanisms remains elusive. Our proteomic analysis identifies valosin-containing protein (VCP) as an mtHtt-binding protein on the mitochondria. Here we show that VCP is selectively translocated to the mitochondria, where it is bound to mtHtt in various HD models. Mitochondria-accumulated VCP elicits excessive mitophagy, causing neuronal cell death. Blocking mtHtt/VCP mitochondrial interaction with a peptide, HV-3, abolishes VCP translocation to the mitochondria, corrects excessive mitophagy and reduces cell death in HD mouse- and patient-derived cells and HD transgenic mouse brains...
August 26, 2016: Nature Communications
https://www.readbyqxmd.com/read/27531396/transient-cerebellar-alterations-during-development-prior-to-obvious-motor-phenotype-in-a-mouse-model-of-spinocerebellar-ataxia-type-6
#13
Sriram Jayabal, Lovisa Ljungberg, Alanna J Watt
KEY POINTS: Spinocerebellar ataxia type 6 (SCA6) is a midlife-onset neurodegenerative disease caused by a CACNA1A mutation; CACNA1A is also implicated in cerebellar development. We have previously shown that when disease symptoms are present in midlife in SCA6(84Q/84Q) mice, cerebellar Purkinje cells spike with reduced rate and precision. In contrast, we find that during postnatal development (P10-13), SCA6(84Q/84Q) Purkinje cells spike with elevated rate and precision. Although surplus climbing fibres are linked to ataxia in other mouse models, we found surplus climbing fibre inputs on developing (P10-13) SCA6(84Q/84Q) Purkinje cells when motor deficits were not detected...
August 17, 2016: Journal of Physiology
https://www.readbyqxmd.com/read/27494522/comparative-analysis-of-pain-behaviours-in-humanized-mouse-models-of-sickle-cell-anemia
#14
Jianxun Lei, Barbara Benson, Huy Tran, Solomon F Ofori-Acquah, Kalpna Gupta
Pain is a hallmark feature of sickle cell anemia (SCA) but management of chronic as well as acute pain remains a major challenge. Mouse models of SCA are essential to examine the mechanisms of pain and develop novel therapeutics. To facilitate this effort, we compared humanized homozygous BERK and Townes sickle mice for the effect of gender and age on pain behaviors. Similar to previously characterized BERK sickle mice, Townes sickle mice show more mechanical, thermal, and deep tissue hyperalgesia with increasing age...
2016: PloS One
https://www.readbyqxmd.com/read/27374878/differential-effects-of-altered-patterns-of-movement-and-strain-on-joint-cell-behaviour-and-skeletal-morphogenesis
#15
L H Brunt, R E H Skinner, K A Roddy, N M Araujo, E J Rayfield, C L Hammond
OBJECTIVE: There is increasing evidence that joint shape is a potent predictor of osteoarthritis (OA) risk; yet the cellular events underpinning joint morphogenesis remain unclear. We sought to develop a genetically tractable animal model to study the events controlling joint morphogenesis. DESIGN: Zebrafish larvae were subjected to periods of flaccid paralysis, rigid paralysis or hyperactivity. Immunohistochemistry and transgenic reporters were used to monitor changes to muscle and cartilage...
November 2016: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/27329763/a-transgenic-mouse-expressing-chmp2bintron5-mutant-in-neurons-develops-histological-and-behavioural-features-of-amyotrophic-lateral-sclerosis-and-frontotemporal-dementia
#16
Aurélia Vernay, Ludivine Therreau, Béatrice Blot, Valérie Risson, Sylvie Dirrig-Grosch, Robin Waegaert, Thiebault Lequeu, François Sellal, Laurent Schaeffer, Rémy Sadoul, Jean-Philippe Loeffler, Frédérique René
Mutations in the charged multivesicular body protein 2B (CHMP2B) are associated with frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), and with a mixed ALS-FTD syndrome. To model this syndrome, we generated a transgenic mouse line expressing the human CHMP2B(intron5) mutant in a neuron-specific manner. These mice developed a dose-dependent disease phenotype. A longitudinal study revealed progressive gait abnormalities, reduced muscle strength and decreased motor coordination. CHMP2B(intron5) mice died due to generalized paralysis...
August 1, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27308892/cognition-enhancing-effect-of-the-aqueous-extract-of-cinnamomum-zeylanicum-on-non-transgenic-alzheimer-s-disease-rat-model-biochemical-histological-and-behavioural-studies
#17
Sowmya Madhavadas, Sarada Subramanian
OBJECTIVE: Several dietary supplements are actively being tested for their dual role of alleviating the metabolic perturbations and restricting the consequent cognitive dysfunctions seen in neurodegenerative disorders such as Alzheimer's disease (AD). The aim of the current study was to assess the influence of aqueous extract of cinnamon (CE) on the monosodium glutamate-induced non-transgenic rat model of AD (NTAD) established with insulin resistance, hyperglycaemia, neuronal loss, and cognitive impairment at a very early stage of life...
June 16, 2016: Nutritional Neuroscience
https://www.readbyqxmd.com/read/27297240/tauopathy-induced-by-low-level-expression-of-a-human-brain-derived-tau-fragment-in-mice-is-rescued-by-phenylbutyrate
#18
Marie K Bondulich, Tong Guo, Christopher Meehan, John Manion, Teresa Rodriguez Martin, Jacqueline C Mitchell, Tibor Hortobagyi, Natalia Yankova, Virginie Stygelbout, Jean-Pierre Brion, Wendy Noble, Diane P Hanger
Human neurodegenerative tauopathies exhibit pathological tau aggregates in the brain along with diverse clinical features including cognitive and motor dysfunction. Post-translational modifications including phosphorylation, ubiquitination and truncation, are characteristic features of tau present in the brain in human tauopathy. We have previously reported an N-terminally truncated form of tau in human brain that is associated with the development of tauopathy and is highly phosphorylated. We have generated a new mouse model of tauopathy in which this human brain-derived, 35 kDa tau fragment (Tau35) is expressed in the absence of any mutation and under the control of the human tau promoter...
August 2016: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/27235359/proteinase-activated-receptor-2-is-involved-in-the-behavioural-changes-associated-with-sickness-behaviour
#19
Roua Abulkassim, Ros Brett, Scott M MacKenzie, Trevor J Bushell
Proteinase-activated receptor-2 (PAR2) is widely expressed in the CNS but whether it plays a key role in inflammation-related behavioural changes remains unknown. Hence, in the present study we have examined whether PAR2 contributes to behaviour associated with systemic inflammation using PAR2 transgenic mice. The onset of sickness behaviour was delayed and the recovery accelerated in PAR2(-/-) mice in the LPS-induced model of sickness behaviour. In contrast, PAR2 does not contribute to behaviour under normal conditions...
June 15, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/27198167/cellular-and-circuit-mechanisms-underlying-spinocerebellar-ataxias
#20
Pratap Meera, Stefan M Pulst, Thomas S Otis
Degenerative ataxias are a common form of neurodegenerative disease that affect about 20 individuals per 100,000. The autosomal dominant spinocerebellar ataxias (SCAs) are caused by a variety of protein coding mutations (single nucleotide changes, deletions and expansions) in single genes. Affected genes encode plasma membrane and intracellular ion channels, membrane receptors, protein kinases, protein phosphatases and proteins of unknown function. Although SCA-linked genes are quite diverse they share two key features: first, they are highly, although not exclusively, expressed in cerebellar Purkinje neurons (PNs), and second, when mutated they lead ultimately to the degeneration of PNs...
August 15, 2016: Journal of Physiology
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