biostudies-literatureRussell NDNIDDK NIH HHSNIH NIGMS R35NIH, Interdisciplinary Training Grant T32 Program in Computational Approaches to Diabetes and Metabolism ResearchNIGMS NIH HHSGlenn Award from the Glenn Foundation for Medical Research, and the University of Utah Mario R Capecchi Endowed Chair in Geneticsjkac104https://www.ebi.ac.uk/biostudies/studies/S-EPMC9157157biostudies-literatureUnknown12(6)The genetic regulation of gene expression varies greatly across tissue-type and individuals and can be strongly influenced by the environment. Many variants, under healthy control conditions, may be silent or even have the opposite effect under diseased stress conditions. This study uses an in vivo mouse model to investigate how the effect of genetic variation changes with cellular stress across different tissues. Endoplasmic reticulum stress occurs when misfolded proteins accumulate in the endoplasmic reticulum. This triggers the unfolded protein response, a large transcriptional response which attempts to restore homeostasis. This transcriptional response, despite being a conserved, basic cellular process, is highly variable across different genetic backgrounds, making it an ideal systemG3 (Bethesda, Md.)The dynamic effect of genetic variation on the in vivo ER stress transcriptional response in different tissues.PMC9157157T32DK110966R35GM124780T32 DK110966R35 GM124780Chow CYRussell NDfalseThe dynamic effect of genetic variation on the in vivo ER stress transcriptional response in different tissues.The genetic regulation of gene expression varies greatly across tissue-type and individuals and can be strongly influenced by the environment. Many variants, under healthy control conditions, may be silent or even have the opposite effect under diseased stress conditions. This study uses an in vivo mouse model to investigate how the effect of genetic variation changes with cellular stress across different tissues. Endoplasmic reticulum stress occurs when misfolded proteins accumulate in the endoplasmic reticulum. This triggers the unfolded protein response, a large transcriptional response which attempts to restore homeostasis. This transcriptional response, despite being a conserved, basic cellular process, is highly variable across different genetic backgrounds, making it an ideal system2022-01-01T00:00:00Z2022 May2026-05-27T20:31:41.003Z2025-02-19T02:44:30.926ZS-EPMC91571573548594510.1093/g3journal/jkac104