Transcriptomics

Dataset Information

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Transcription profiling by array of mouse cerebellum mutant for Pon1 after treatment with chlorpyrifos


ABSTRACT: Chlorpyrifos (CPF) is an organophosphorus (OP) insecticide that is still widely used despite statutory restrictions on home use. CPF is converted to chlorpyrifos oxon (CPO) by oxidative desulfuration in liver. Paraoxonase (PON1) polymorphisms affects the catalytic efficiency of the hydrolysis of OPs, including CPO. We used both wt (PON1+/+) and PON1 knockout (PON1-/-) mice and PON1-/- mice carrying transgenes encoding the human alloforms tgHuPON1Q192 and tgHuPON1R192 to gain insight into the mechanisms of neurotoxicity of CPO throughout postnatal development, and to ascertain the importance of the PON1Q192R polymorphism for protecting against developmental toxicity of CPO. Whole-genome microarrays were used to measure gene expression changes associated with chronic CPO exposure of developing (PND 4-21) PON1-/-, tgHuPON1Q192R transgenic and PON1+/+ mice. Expression profiles are derived from cerebella from wild-type C57/Bl6 and PON1-/- on a C57/Bl6 background and two transgenic strains (tgHuPON1Q192, tgHuPON1R192) expressing either human PON1Q192 or human PON1R192 on the PON1-/- C57/Bl6 background. The mice were subjected to chronic postnatal exposure to CPO (CPO). Transgenic, PON1-KO and WT neonatal mice either treated with control (DMSO), 0.35 mg*kg-1*day-1 CPO or 0.5 mg*kg-1*day-1 CPO daily from PND 4 to PND 21. Chlorpyrifos (CPF) is converted to chlorpyrifos oxon (CPO) by oxidative desulfuration in liver. 55 arrays, 12 experimental groups (strain + treatment), due to QC issues the replicates are as follows; PON1-KO-0.35 (5), PON1-KO-.O5 (3), PON1-KO-DMSO (4), PON1-Q129-0.35 (5), PON1-Q129-0.5 (5), PON1-Q129-DMSO (4), PON1-R129-0.35 (5), PON1-R129-0.5 (5), PON1-R129-DMSO (4), WT-0.35 (6), WT-0.5 (3), WT-DMSO (6)

REANALYSED by: E-GEOD-25250

ORGANISM(S): Mus musculus  

SUBMITTER: Federico M Farin  Michael Coon   Sarah S Park   Theodor K Bammler   Richard P Beyer   Lucio G Costa   Toby B Cole   Clement E Furlong    

PROVIDER: E-GEOD-25250 | ArrayExpress | 2011-11-09

SECONDARY ACCESSION(S): GSE25250PRJNA134671

REPOSITORIES: GEO, ArrayExpress

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Publications

Repeated developmental exposure of mice to chlorpyrifos oxon is associated with paraoxonase 1 (PON1)-modulated effects on cerebellar gene expression.

Cole Toby B TB   Beyer Richard P RP   Bammler Theo K TK   Park Sarah S SS   Farin Federico M FM   Costa Lucio G LG   Furlong Clement E CE  

Toxicological sciences : an official journal of the Society of Toxicology 20110614 1


Microarray analysis was used to examine effects of repeated postnatal exposure to chlorpyrifos oxon (CPO) on gene expression in the cerebellum of genetically modified mice. The high-density lipoprotein-associated enzyme paraoxonase 1 (PON1) plays a significant role in the detoxication of CPO, which is present in exposures and generated from chlorpyrifos (CPF) in vivo following exposure. Two factors are important in modulating toxicity of CPO, the Q192R PON1 polymorphism and PON1 plasma level, wh  ...[more]

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