ORCID Profile
0000-0002-6085-7773
Current Organisation
University of Sydney
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Publisher: Elsevier BV
Date: 07-2020
Publisher: American Thoracic Society
Date: 15-10-2011
Publisher: Elsevier BV
Date: 06-2020
Publisher: Wiley
Date: 26-10-2015
DOI: 10.1002/JNR.23679
Publisher: IOP Publishing
Date: 15-03-2021
Publisher: IEEE
Date: 07-2020
Publisher: Springer Science and Business Media LLC
Date: 23-05-2019
Publisher: Cold Spring Harbor Laboratory
Date: 10-07-2023
DOI: 10.1101/2023.07.08.548198
Abstract: Self-grooming behavior in rodents serves as a valuable model for investigating stereotyped and perseverative responses. Most current grooming analyses primarily rely on video observation, which lacks standardization, efficiency, and quantitative information about force. To address these limitations, we developed an automated paradigm to analyze grooming using a force-plate actometer. Grooming behavior is quantified by calculating ratios of relevant movement power spectral bands. These ratios are then input into a naïve Bayes classifier, trained with manual video observations. To validate the effectiveness of this method, we applied it to the behavioral analysis of the early-life striatal cholinergic interneuron depletion (CIN-d) mouse, a model of tic pathophysiology recently developed in our laboratory, which exhibits prolonged grooming responses to acute stressors. Behavioral monitoring was simultaneously conducted on the force-place actometer and by video recording. The naïve Bayes approach achieved 93.7% accurate classification and an area under the receiver operating characteristic curve of 0.894. We confirmed that male CIN-d mice displayed significantly longer grooming durations compared to controls. However, this elevation was not correlated with increases in grooming force. Notably, haloperidol, a benchmark therapy for tic disorders, reduced both grooming force and duration. In contrast to observation-based approaches, our method affords rapid, unbiased, and automated assessment of grooming duration, frequency, and force. Our novel approach enables fast and accurate automated detection of grooming behaviors. This method holds promise for high-throughput assessments of grooming stereotypies in animal models of tic disorders and other psychiatric conditions.
Publisher: Cold Spring Harbor Laboratory
Date: 29-03-2022
DOI: 10.1101/2022.03.28.486143
Abstract: The shaker rat carries a naturally occurring mutation leading to progressive ataxia characterized by Purkinje cell (PC) loss. We previously reported on fine-mapping the shaker locus to the long arm of the rat X chromosome. In this work, we sought to identify the mutated gene underlying the shaker phenotype and confirm its identity by functional complementation. We fine-mapped the candidate region and analyzed cerebellar transcriptomes to identify deleterious variants. We generated an adeno-associated virus (AAV) targeting solute carrier family 9, member A6 ( Slc9a6) expression to PCs using a mouse L7-6 (L7) promoter, as well as a control green fluorescent protein (GFP)-expressing virus. We administered AAVs prior to the onset of PC degeneration through intracerebroventricular injection and evaluated the molecular, cellular, and motor phenotypes. We identified a XM_217630.9 ( Slc9a6 ):c.[191_195delinsA] variant in the Slc9a6 gene that segregated with disease. This mutation is predicted to generate a truncated sodium-hydrogen exchanger 6 (NHE6) protein, p.(Ala64Glufs*23). Administration of AAV9-PHP.eB expressing rat Slc9a6 prior to symptom onset reduced the shaker motor, molecular, and cellular phenotypes. Slc9a6 is mutated in shaker and also in human Christianson syndrome, an epileptic encephalopathy. AAV-based gene therapy may be a viable therapeutic strategy for Christianson syndrome, and the shaker rat model may aid in therapeutic development.
Publisher: Wiley
Date: 09-2020
DOI: 10.1002/JPEN.1990
Publisher: Springer Science and Business Media LLC
Date: 17-05-2023
Publisher: Cold Spring Harbor Laboratory
Date: 17-11-2022
DOI: 10.1101/2022.11.16.516816
Abstract: Staufen1 (STAU1) is a multifunctional RNA binding protein that controls mRNA degradation and subcellular localization. STAU1 interacts with the ATXN2 protein, that is polyglutamine expanded in spinocerebellar ataxia type 2 (SCA2). We previously showed that STAU1 is elevated and aggregated in cells from SCA2 patients, cells from amyotrophic lateral sclerosis (ALS) patients, and in SCA2 and ALS mouse models. We also found that reduction of STAU1 abundance in vivo by genetic interaction improved motor behavior in an SCA2 mouse model, normalized the levels of several SCA2-related proteins, and reduced aggregation of polyglutamine-expanded ATXN2. Here we developed antisense oligonucleotides (ASOs) lowering STAU1 expression toward developing a therapeutic that may be effective for treating SCA2 and ALS. We performed a screen of 118 20mer phosphorothioate 2’- O -methoxyethyl (MOE) ASO gapmers targeting across the STAU1 mRNA coding region for lowering STAU1 expression in HEK-293 cells. ASO hits lowering STAU1 by % were rescreened in SCA2 patient fibroblasts, and 10 of these were tested for lowering STAU1 abundance in vivo in a new BAC-STAU1 mouse model. This identified efficacious ASOs targeting human STAU1 in vivo that normalized autophagy marker proteins, including ASO-45 that also targets mouse Stau1 . When delivered by intracerebroventricular (ICV) injection, ASO-45 normalized autophagy markers and abnormal mRNA abundances in cerebella of ATXN2-Q127 SCA2 mice, as well as ChAT, NeuN and cleaved caspase-3 in spinal cord of Thy1- TDP-43 transgenic mice. Targeting STAU1 may be an effective strategy for treating ALS and SCA2 as well as other disorders characterized by its overabundance.
Publisher: Oxford University Press (OUP)
Date: 09-01-2022
DOI: 10.1093/HMG/DDAD004
Abstract: The shaker rat carries a naturally occurring mutation leading to progressive ataxia characterized by Purkinje cell (PC) loss. We previously reported on fine-mapping the shaker locus to the long arm of the rat X chromosome. In this work, we sought to identify the mutated gene underlying the shaker phenotype and confirm its identity by functional complementation. We fine-mapped the candidate region and analyzed cerebellar transcriptomes, identifying a XM_217630.9 (Slc9a6):c.[191_195delinsA] variant in the Slc9a6 gene that segregated with disease. We generated an adeno-associated virus (AAV) targeting Slc9a6 expression to PCs using the mouse L7–6 (L7) promoter. We administered the AAV prior to the onset of PC degeneration through intracerebroventricular injection and found that it reduced the shaker motor, molecular and cellular phenotypes. Therefore, Slc9a6 is mutated in shaker and AAV-based gene therapy may be a viable therapeutic strategy for Christianson syndrome, also caused by Slc9a6 mutation.
Publisher: Wiley
Date: 16-04-2019
DOI: 10.1002/ANA.25464
Publisher: Frontiers Media SA
Date: 06-07-2015
No related grants have been discovered for Collin Anderson.