mRNA levels in control rat liver display strain-specific, hereditary, and AHR-dependent components.

Rat is a major model organism in toxicogenomics and pharmacogenomics. Hepatic mRNA profiles after treatment with xenobiotic chemicals are used to predict and understand drug toxicity and mechanisms. Surprisingly, neither inter- and intra-strain variability of mRNA abundances in control rats nor the...

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Autores principales:	Paul C Boutros, Ivy D Moffat, Allan B Okey, Raimo Pohjanvirta
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/830cde9a27824d7ba7a9e2b831c15394
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spelling	oai:doaj.org-article:830cde9a27824d7ba7a9e2b831c153942021-11-18T06:50:35ZmRNA levels in control rat liver display strain-specific, hereditary, and AHR-dependent components.1932-620310.1371/journal.pone.0018337https://doaj.org/article/830cde9a27824d7ba7a9e2b831c153942011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21760882/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Rat is a major model organism in toxicogenomics and pharmacogenomics. Hepatic mRNA profiles after treatment with xenobiotic chemicals are used to predict and understand drug toxicity and mechanisms. Surprisingly, neither inter- and intra-strain variability of mRNA abundances in control rats nor the heritability of rat mRNA abundances yet been established. We address these issues by studying five populations: the popular Sprague-Dawley strain, sub-strains of Long-Evans and Wistar rats, and two lines derived from crosses between the Long-Evans and Wistar sub-strains. Using three independent techniques--variance analysis, linear modelling, and unsupervised pattern recognition--we characterize extensive intra- and inter-strain variability in mRNA levels. We find that both sources of variability are non-random and are enriched for specific functional groups. Specific transcription-factor binding-sites are enriched in their promoter regions and these genes occur in "islands" scattered throughout the rat genome. Using the two lines generated by crossbreeding we tested heritability of hepatic mRNA levels: the majority of rat genes appear to exhibit directional genetics, with only a few interacting loci. Finally, a comparison of inter-strain heterogeneity between mouse and rat orthologs shows more heterogeneity in rats than mice; thus rat and mouse heterogeneity are uncorrelated. Our results establish that control hepatic mRNA levels are relatively homogeneous within rat strains but highly variable between strains. This variability may be related to increased activity of specific transcription-factors and has clear functional consequences. Future studies may take advantage of this phenomenon by surveying panels of rat strains.Paul C BoutrosIvy D MoffatAllan B OkeyRaimo PohjanvirtaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 7, p e18337 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Paul C Boutros Ivy D Moffat Allan B Okey Raimo Pohjanvirta mRNA levels in control rat liver display strain-specific, hereditary, and AHR-dependent components.
description	Rat is a major model organism in toxicogenomics and pharmacogenomics. Hepatic mRNA profiles after treatment with xenobiotic chemicals are used to predict and understand drug toxicity and mechanisms. Surprisingly, neither inter- and intra-strain variability of mRNA abundances in control rats nor the heritability of rat mRNA abundances yet been established. We address these issues by studying five populations: the popular Sprague-Dawley strain, sub-strains of Long-Evans and Wistar rats, and two lines derived from crosses between the Long-Evans and Wistar sub-strains. Using three independent techniques--variance analysis, linear modelling, and unsupervised pattern recognition--we characterize extensive intra- and inter-strain variability in mRNA levels. We find that both sources of variability are non-random and are enriched for specific functional groups. Specific transcription-factor binding-sites are enriched in their promoter regions and these genes occur in "islands" scattered throughout the rat genome. Using the two lines generated by crossbreeding we tested heritability of hepatic mRNA levels: the majority of rat genes appear to exhibit directional genetics, with only a few interacting loci. Finally, a comparison of inter-strain heterogeneity between mouse and rat orthologs shows more heterogeneity in rats than mice; thus rat and mouse heterogeneity are uncorrelated. Our results establish that control hepatic mRNA levels are relatively homogeneous within rat strains but highly variable between strains. This variability may be related to increased activity of specific transcription-factors and has clear functional consequences. Future studies may take advantage of this phenomenon by surveying panels of rat strains.
format	article
author	Paul C Boutros Ivy D Moffat Allan B Okey Raimo Pohjanvirta
author_facet	Paul C Boutros Ivy D Moffat Allan B Okey Raimo Pohjanvirta
author_sort	Paul C Boutros
title	mRNA levels in control rat liver display strain-specific, hereditary, and AHR-dependent components.
title_short	mRNA levels in control rat liver display strain-specific, hereditary, and AHR-dependent components.
title_full	mRNA levels in control rat liver display strain-specific, hereditary, and AHR-dependent components.
title_fullStr	mRNA levels in control rat liver display strain-specific, hereditary, and AHR-dependent components.
title_full_unstemmed	mRNA levels in control rat liver display strain-specific, hereditary, and AHR-dependent components.
title_sort	mrna levels in control rat liver display strain-specific, hereditary, and ahr-dependent components.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/830cde9a27824d7ba7a9e2b831c15394
work_keys_str_mv	AT paulcboutros mrnalevelsincontrolratliverdisplaystrainspecifichereditaryandahrdependentcomponents AT ivydmoffat mrnalevelsincontrolratliverdisplaystrainspecifichereditaryandahrdependentcomponents AT allanbokey mrnalevelsincontrolratliverdisplaystrainspecifichereditaryandahrdependentcomponents AT raimopohjanvirta mrnalevelsincontrolratliverdisplaystrainspecifichereditaryandahrdependentcomponents
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mRNA levels in control rat liver display strain-specific, hereditary, and AHR-dependent components.

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