A5019760593- 3D Printing in Biomedical Research
- Neuroendocrine regulation and behavior
- Circadian rhythm and melatonin
- Zebrafish Biomedical Research Applications
- RNA regulation and disease
- Adipose Tissue and Metabolism
- Genetics and Neurodevelopmental Disorders
- Neuroscience and Neuropharmacology Research
- Animal Behavior and Welfare Studies
- Food Supply Chain Traceability
- Video Surveillance and Tracking Methods
- Congenital heart defects research
- Regulation of Appetite and Obesity
- Biochemical Analysis and Sensing Techniques
- RNA Research and Splicing
- Cell Image Analysis Techniques
- Neuroinflammation and Neurodegeneration Mechanisms
- Economic and Financial Impacts of Cancer
- Animal testing and alternatives
- Amyotrophic Lateral Sclerosis Research
- Health Systems, Economic Evaluations, Quality of Life
- Pain Mechanisms and Treatments
- Human Pose and Action Recognition
- Sleep and Wakefulness Research
- Mitochondrial Function and Pathology
Mary Lyon Centre at MRC Harwell
2017-2024
Medical Research Council
2016-2024
University of Portsmouth
2012-2013
University of Sunderland
2012
Meharry Medical College
2002
An important factor in reducing variability mouse test outcomes has been to develop assays that can be used for continuous automated home cage assessment. Our experience shown this most evidenced long-term assessment of wheel-running activity mice. Historically, mice and other rodents have as a robust assay determine, with precision, the inherent period circadian rhythms Furthermore, instrumental dissecting molecular genetic basis mammalian rhythms. In teasing out elements determined its...
Central nervous system disorders such as autism well the range of neurodegenerative diseases Huntington's disease are commonly investigated using genetically altered mouse models. The current for characterizing these mice usually involves removing animals from their home-cage environment and placing them into novel environments where they undergo a battery tests measuring behavioral physical phenotypes. These often only conducted short periods times in social isolation. However, human...
Abstract Intracerebral injection of ibotenate into mouse pups induced grey matter lesions and white cysts; co‐administration brain‐derived neurotrophic factor (BDNF) produced a dose‐dependent reduction in these lesions. In contrast, glial cell line‐derived (GDNF) had no significant effect, whereas nerve growth (NGF) or interleukin‐1β (IL‐1β) resulted exacerbation. The neuroprotective effects BDNF were abolished by anti‐BDNF antibody MEK inhibitors, ABT‐737, BH3 mimetic Bcl‐2 antagonist....
Spinocerebellar ataxias (SCAs) are autosomal dominantly inherited neurodegenerative disorders with no effective treatment. Aberrant signalling through the metabotropic glutamate receptor (mGluR1) has been implicated in several SCAs. However, whether disease is caused decreased or increased mGluR1 remains controversial. Here, we generate first mouse model of enhanced function by introducing a gain-of-function mutation (p.Y792C) that causes SCA44 1 (Grm1) gene. Grm1 mutant mice recapitulate...
Loss-of-function mutations in a human AMPA receptor-associated protein, ferric chelate reductase 1-like (FRRS1L), are associated with devastating neurological condition incorporating choreoathetosis, cognitive deficits and epileptic encephalopathies. Furthermore, evidence from overexpression ex vivo studies has implicated FRRS1L receptor biogenesis, suggesting that changes glutamatergic signalling might underlie the disorder. Here, we investigated neurobehavioural correlates of disorder...
Monitoring the activity of mice within their home cage is proving to be a powerful tool for revealing subtle and early-onset phenotypes in mouse models. Video-tracking, particular, lends itself automated machine-learning technologies that have potential improve manual annotations carried out by humans. This type recording analysis particularly objective phenotyping, monitoring behaviors with no experimenter intervention. Automated home-cage testing allows non-evoked voluntary behaviors,...
Although activation of alpha(2)-adrenoceptors is known to play an important role in mediating antinociception, the contribution various alpha(2)-adrenoceptor subtypes modulating trigeminal nociception remains unknown since subtype specific agonists and antagonists are not available. The present study investigated functional N-methyl-D-aspartate-induced nociceptive behavior medullary dorsal horn by using antisense oligodeoxynucleotides selectively knock-down receptor subtypes. Microinjection...
A noninvasive sleep screen uncovers a Vamp2 mouse mutation with synaptic deficits underlying substantial disturbances.
Abstract Over the last century, study of mouse behavior has uncovered insights into brain molecular mechanisms while revealing potential causes many neurological disorders. To this end, researchers have widely exploited use mutant strains, including those generated in mutagenesis screens and produced using increasingly sophisticated genome engineering technologies. It is now relatively easy to access models carrying alleles that faithfully recapitulate changes found human patients or bearing...
Genetic studies in obese rodents and humans can provide novel insights into the mechanisms involved energy homeostasis. In this study, we genetically mapped chromosomal region underlying development of severe obesity a mouse line identified as part dominant N-ethyl-N-nitrosourea (ENU) mutagenesis screen. We characterized metabolic behavioral phenotype mutant mice examined changes hypothalamic gene expression. humans, genetic data from people with early onset obesity. an heterozygous for...
Circadian rhythms persist in almost all organisms and are crucial for maintaining appropriate timing physiology behaviour. Here, we describe a mouse mutant where the central mammalian pacemaker, suprachiasmatic nucleus (SCN), has been genetically ablated by conditional deletion of transcription factor Zfhx3 developing hypothalamus. Mutants were arrhythmic over light-dark cycle constant darkness. Moreover, metabolic parameters vivo although molecular oscillations liver maintained some...
Abstract Behavioural experiments often happen in specialised arenas, but this may confound the analysis. To address issue, we provide tools to study mice home-cage environment, equipping biologists with possibility capture temporal aspect of individual’s behaviour and model interaction interdependence between cage-mates minimal human intervention. Our main contribution is novel Global Behaviour Model (GBM) which summarises joint groups across cages, using a permutation matrix match mouse...
<ns4:p><ns4:bold>Background: </ns4:bold>The environmental housing conditions of laboratory animals are important for both welfare and reliable, reproducible data. Guidelines currently exist factors such as lighting cycles, temperature, humidity, noise, however, the latter current guidelines may overlook details. In case most common species, mouse, range frequencies they can hear is far higher than that humans. The briefly mention ultrasonic (>20 kHz) adversely affect mice, acoustic...
ABSTRACT Variants in the ubiquitously expressed DNA/RNA-binding protein FUS cause aggressive juvenile forms of amyotrophic lateral sclerosis (ALS). Most mutation studies have focused on motor neuron degeneration; little is known about wider systemic or developmental effects. We studied pleiotropic phenotypes a physiological knock-in mouse model carrying pathogenic FUSDelta14 homozygosity. RNA sequencing multiple organs aimed to identify pathways altered by mutant transcriptome, including...
Identifying the genetic determinants of pain is a scientific imperative given magnitude global health burden that causes. Here, we report screen for nociception, performed under auspices International Mouse Phenotyping Consortium. A biased set 110 single-gene knockout mouse strains was screened 1 or more nociception and hypersensitivity assays, including chemical (formalin) mechanical thermal (von Frey filaments Hargreaves tests, respectively), with without an inflammatory agent (complete...
This paper presents a spatiotemporal deep learning approach for mouse behavioral classification in the home-cage. Using series of dual-stream architectures with assorted modifications optimal performance, we introduce novel feature sharing that jointly processes streams at regular intervals throughout network. The dataset focus is an annotated, publicly available singly-housed mouse. We achieved even better accuracy by ensembling best performing models; Inception-based network and...
Highlights•Hyperactivity associated with moderate hearing loss in ENU-induced whirlin mutant•Overexpression of C-terminus the brain rescues hyperactive behaviors•Transcriptional profile across tissues underscores pleiotropy•Qualitative deficit temporal processing acoustic stimulusSummaryDespite some evidence indicating diverse roles neurons, functional corollary gene function and behavior has not been investigated or broadly characterized. A single nucleotide variant was identified from our...
Abstract Genome-wide association studies (GWAS) have identified a transcriptional network of Alzheimer’s disease (AD) risk genes that are primarily expressed in microglia and associated with AD pathology. However, traditional short-read sequencers limited our ability to fully characterize how GWAS variants exert their effects on gene expression regulation or alternative splicing response the pathology, particularly resulting inaccurate detection splicing. To address this gap, we utilized...