GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE247nnn/GSE247877/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE247877GEOGSEfalseEffect of monomethylarsonous acid (MMAIII) on primary fibroblasts in vitro derived from Diversity Outbred (DO) mice aged 4-6 weeksGenetically diverse cell populations derived from mice are powerful tools for studying gene-environment interactions. Using fibroblasts derived from Diversity Outbred (DO) mice, we performed a high-content screen (HCS) of cell morphology changes to the oxidative stress and DNA damage-inducing arsenic metabolite monomethylarsonous acid (MMAIII). We show that fibroblast morphological changes in response to increasing MMAIII exposure can be modeled using dose-response modeling. We use dose-response model parameters (i.e., EC50) as traits to map cell morphology quantitative trait loci (QTL) in response to MMAIII exposure. We find that dose-response cmQTLs overlap many known genes associated with arsenic susceptibility, including Abcc4 and Txnrd1, and also represent novel targets, including Xrcc2. Moreover, we show that the cmQTL effects are reproducible and how mouse genetics can be leveraged in a systems toxicological approach to find candidate genes and support experimental validation. In summary, our work demonstrates that cmQTLs reflect the key molecular events that are known to occur during acute arsenic exposure, which are adaptable across chemicals and cell culture models.2023/11/19GSE247877GSM7902559GSM7902558GSM7902557GSM7902556GSM7902555GSM7902554GSM7902553GSM7902552GSM7902551GSM7902572GSM7902550GSM7902571GSM7902570GSM7902549GSM7902548GSM7902569GSM7902547GSM7902546GSM7902568GSM7902567GSM7902545GSM7902566GSM7902544GSM7902543GSM7902565GSM7902564GSM7902542GSM7902563GSM7902541GSM7902562GSM7902561GSM790256024247247877Mus musculus