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Series GSE168210 Query DataSets for GSE168210
Status Public on Aug 05, 2021
Title Paraoxonase 2 Deficiency in Mice Alters Motor Behavior and Causes Region-Specific Transcript Changes in the Brain
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Araoxonase 2 (PON2) is an intracellular antioxidant enzyme shown to play an important role in mitigating oxidative stress in the brain. Oxidative stress is a common mechanism of toxicity for neurotoxicants and is increasingly implicated in the etiology of multiple neurological diseases. While PON2 deficiency increases oxidative stress in the brain in-vitro, little is known about its effects on behavior in-vivo and what global transcript changes occur from PON2 deficiency. Therefore, we sought to characterize the effects of PON2 deficiency on behavior in mice, with an emphasis on locomotion, and evaluate transcriptional changes with RNA-Seq. Behavioral endpoints included home-cage behavior (Noldus PhenoTyper), motor coordination (Rotarod) and various gait metrics (Noldus CatWalk). Home-cage behavior analysis showed PON2 deficient mice had increased activity at night compared to wildtype controls and spent more time in the center of the cage, displaying a possible anxiolytic phenotype. PON2 deficient mice had significantly shorter latency to fall when tested on the rotarod, suggesting impaired motor coordination. Minimal gait alterations were observed, with decreased girdle support posture noted as the only significant change with PON2 deficiency. Finally, A subset of samples were utilized for RNA-Seq analysis, looking at three discrete brain regions: cerebral cortex, striatum and cerebellum. Highly regional- and sex-specific changes in RNA expression were found when comparing PON2 deficient and wildtype mice, suggesting PON2 may play distinct regional roles in the brain in a sex-specific manner. Taken together, these findings demonstrates that PON2 deficiency significantly alters the brain on both a biochemical and phenotypic level, with a specific impact on motor function. This data has implications for future gene-environment toxicological studies and warrants further investigation of PON2 in the brain.
 
Overall design Male and female wildtype (WT) and PON2 deficient (PON2-def) mice (Ng et al., 2006) on a C57BL/6J background were used for this study. Seven to ten animals were used per sex per group. Mice were bred from PON2 deficient heterozygous crosses with resulting WT and PON2-def homozygous littermates used in rolling cohorts. Behavioral testing began at 3 – 4 months of age. Mice were housed in a specific pathogen-free facility on a 14-hour light/ 10-hour dark cycle with ad libitum access to food and water. All procedures were conducted in accordance with the National Institute of Health Guide for the Use and Care of Laboratory Animals and were approved by the University of Washington Institutional Animal Care and Use Committee. Mice were sacrificed at 3 – 4 months of age upon conclusion of behavioral testing. Cerebral cortex, striatum and cerebellum were fresh dissected (Spijker 2011) and flash frozen in liquid nitrogen. Tissue was pulverized with a pre-chilled mortar and pestle into a fine powder, stored at −80°C and aliquoted into appropriate buffers for downstream testing.
 
Contributor(s) Garrick JM, Cole TB, Bammler TK, MacDonald JW, Marsillach J, Furlong CE, Costa LG
Citation(s) 34216730
Submission date Mar 03, 2021
Last update date Nov 04, 2021
Contact name James William MacDonald
E-mail(s) jmacdon@uw.edu
Organization name University of Washington
Department Environmental and Occupational Health Sciences
Street address 4225 Roosevelt Way NE
City Seattle
State/province WA
ZIP/Postal code 98105-6099
Country USA
 
Platforms (1)
GPL23479 BGISEQ-500 (Mus musculus)
Samples (60)
GSM5133984 Cortex_F_WT_1
GSM5133985 Cortex_F_WT_2
GSM5133986 Cortex_F_WT_3
Relations
BioProject PRJNA706455
SRA SRP309190

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Supplementary file Size Download File type/resource
GSE168210_counts.txt.gz 9.6 Mb (ftp)(http) TXT
GSE168210_voom_cpm.txt.gz 9.6 Mb (ftp)(http) TXT
GSE168210_voom_weights.txt.gz 9.6 Mb (ftp)(http) TXT
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Processed data are available on Series record

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