UseCases_ArguminSci_Discourse  

PubMed:10434303 JSONTXT 8 Projects

Annnotations TAB TSV DIC JSON TextAE Lectin_function IAV-Glycan

Id Subject Object Predicate Lexical cue
T1 0-141 DRI_Challenge denotes Transgenic mice expressing mutated full-length HD cDNA: a paradigm for locomotor changes and selective neuronal loss in Huntington's disease.
T2 142-396 DRI_Challenge denotes Huntington's disease (HD) is a progressive neurodegenerative disorder characterized clinically by motor and psychiatric disturbances and pathologically by neuronal loss and gliosis (reactive astrocytosis) particularly in the striatum and cerebral cortex.
T3 397-502 DRI_Approach denotes We have recently created HD full-length cDNA transgenic mouse models that may serve as a paradigm for HD.
T4 503-570 DRI_Background denotes A more detailed characterization of these models is presented here.
T5 571-736 DRI_Background denotes The transgene encoding normal huntingtin consists of 9417 bp of the huntingtin coding sequences including 16 tandem CAGs coding for polyglutamines as part of exon 1.
T6 737-804 DRI_Approach denotes The transgene is driven by a heterologous cytomegalovirus promoter.
T7 805-880 DRI_Approach denotes Five independent transgenic mouse lines were obtained using this construct.
T8 881-1035 DRI_Approach denotes An additional six transgenic lines were obtained using full-length HD constructs that have been modified to include either 48 or 89 CAG repeat expansions.
T9 1036-1200 DRI_Outcome denotes Southern blot and densitometric analyses indicated unique integration sites for the transgene in each of the lines with a copy number ranging from two to 22 copies.
T10 1201-1351 DRI_Background denotes Widespread expression of the transgene in brain, heart, spleen, kidney, lung, liver and gonads from each line was determined by Western blot analyses.
T11 1352-1454 DRI_Background denotes In the brain, transgene expression was found in cerebral cortex, striatum, hippocampus and cerebellum.
T12 1455-1547 DRI_Outcome denotes Expression of the transgene was as much as five times the endogenous mouse huntingtin level.
T13 1548-1663 DRI_Outcome denotes Phenotypically, only mice expressing 48 or 89 CAG repeats manifested progressive behavioural and motor dysfunction.
T14 1664-1820 DRI_Background denotes Early behavioural abnormalities were characterized by trunk curling and clasping of both fore- and hindlimbs when the animals were suspended by their tails.
T15 1821-2028 DRI_Background denotes Subsequently, these mice exhibited hyperkinetic movements, including heightened exploratory activities, unidirectional rotational behaviour, backflipping and excessive grooming that lasted for several weeks.
T16 2029-2158 DRI_Background denotes Eventually, the animals progressed to a hypokinetic phase consisting of slowed movements and lack of response to sensory stimuli.
T17 2159-2245 DRI_Background denotes Urine retention or incontinence was also a prominent feature of the hypokinetic phase.
T18 2246-2352 DRI_Approach denotes At the end stage of the disease process, HD48(B,D) and HD89(A-C) mice became akinetic just prior to death.
T19 2353-2527 DRI_Background denotes Neuropathological examination of mice at various stages indicated that it was only during the hypokinetic phase and thereafter when selective neuronal loss was most apparent.
T20 2528-2631 DRI_Background denotes Regions of neurodegeneration and loss included the striatum, cerebral cortex, thalamus and hippocampus.
T21 2632-2712 DRI_Background denotes TUNEL staining indicated an apoptotic mode of cell death in these brain regions.
T22 2713-2880 DRI_Outcome denotes Comparative neuronal counts after Nissl staining showed as much as 20% loss of small and medium neurons in the striatum in mice at the hypokinetic and akinetic stages.
T23 2881-2955 DRI_Background denotes Reactive astrocytosis accompanied the areas of neurodegeneration and loss.
T24 2956-3188 DRI_Background denotes Polyglutamine aggregates in the form of neuronal intranuclear inclusions and diffuse nuclear and perinuclear aggregations were found in a small percentage of neurons, including those in brain regions that are typically spared in HD.
T25 3189-3296 DRI_Outcome denotes This observation suggests that polyglutamine aggregates may not be sufficient to cause neuronal loss in HD.
T26 3297-3534 DRI_Outcome denotes In both behavioural and neuropathological analyses, wild-type and transgenic animals with 16 CAG repeats were indistinguishable from each other and do not exhibit the changes observed for mice carrying the 48 and 89 CAG repeat mutations.
T27 3535-3769 DRI_Challenge denotes Thus, animals expressing the CAG repeat expansions appear to represent clinically analogous models for HD pathogenesis, and may also provide insights into the underlying pathophysiological mechanisms of other triplet repeat disorders.