scholarly journals The Liver X‐Receptor (LXR) gene promoter is hypermethylated in a mouse model of prenatal protein restriction

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Torsten Plosch ◽  
Esther M.E. Straten ◽  
Vincent W. Bloks ◽  
Nicolette C.A. Huijkman ◽  
Folkert Kuipers
Keyword(s):  
Mouse Model ◽  
Gene Promoter ◽  
Liver X Receptor ◽  
Protein Restriction

The liver X-receptor gene promoter is hypermethylated in a mouse model of prenatal protein restriction

2010 ◽  
Vol 298 (2) ◽  
pp. R275-R282 ◽  
Author(s):  
Esther M. E. van Straten ◽  
Vincent W. Bloks ◽  
Nicolette C. A. Huijkman ◽  
Julius F. W. Baller ◽  
Hester van Meer ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Lipid Metabolism ◽  
Target Genes ◽  
Cpg Island ◽  
Fetal Liver ◽  
Gene Promoter ◽  
Liver X Receptor ◽  
Protein Restriction ◽  
Luciferase Expression ◽  
Adult Disease

Prenatal nutrition as influenced by the nutritional status of the mother has been identified as a determinant of adult disease. Feeding low-protein diets during pregnancy in rodents is a well-established model to induce programming events in offspring. We hypothesized that protein restriction would influence fetal lipid metabolism by inducing epigenetic adaptations. Pregnant C57BL/6J mice were exposed to a protein-restriction protocol (9% vs. 18% casein). Shortly before birth, dams and fetuses were killed. To identify putative epigenetic changes, CG-dinucleotide-rich region in the promoter of a gene (CpG island) methylation microarrays were performed on DNA isolated from fetal livers. Two hundred four gene promoter regions were differentially methylated upon protein restriction. The liver X-receptor (Lxr) alpha promoter was hypermethylated in protein-restricted pups. Lxr alpha is a nuclear receptor critically involved in control of cholesterol and fatty acid metabolism. The mRNA level of Lxra was reduced by 32% in fetal liver upon maternal protein restriction, whereas expression of the Lxr target genes Abcg5/ Abcg8 was reduced by 56% and 51%, respectively, measured by real-time quantitative PCR. The same effect, although less pronounced, was observed in the fetal intestine. In vitro methylation of a mouse Lxra-promoter/luciferase expression cassette resulted in a 24-fold transcriptional repression. Our study demonstrates that, in mice, protein restriction during pregnancy interferes with DNA methylation in fetal liver. Lxra is a target of differential methylation, and Lxra transcription is dependent on DNA methylation. It is tempting to speculate that perinatal nutrition may influence adult lipid metabolism by DNA methylation, which may contribute to the epidemiological relation between perinatal/neonatal nutrition and adult disease.

scholarly journals Pharmacologic inhibition of mTORC1 mimics dietary protein restriction in a mouse model of lactation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Virginia L. Pszczolkowski ◽  
Steven J. Halderson ◽  
Emma J. Meyer ◽  
Amy Lin ◽  
Sebastian I. Arriola Apelo
Keyword(s):  
Mouse Model ◽  
Dietary Protein ◽  
Protein Restriction ◽  
Dietary Protein Restriction ◽  
Pharmacologic Inhibition

A Novel Transgenic Mouse Model Reveals Humanlike Regulation of an 8-kbp Human TERT Gene Promoter Fragment in Normal and Tumor Tissues

2005 ◽  
Vol 65 (4) ◽  
pp. 1187-1196 ◽  
Author(s):  
Julia M. Ritz ◽  
Olaf Kühle ◽  
Sabine Riethdorf ◽  
Bence Sipos ◽  
Wolfgang Deppert ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Gene Promoter ◽  
Transgenic Mouse Model ◽  
Promoter Fragment ◽  
Tumor Tissues ◽  
Tert Gene

scholarly journals The Liver X Receptor Ligand T0901317 Decreases Amyloid β Productionin Vitroand in a Mouse Model of Alzheimer's Disease

2004 ◽  
Vol 280 (6) ◽  
pp. 4079-4088 ◽  
Author(s):  
Radosveta P. Koldamova ◽  
Iliya M. Lefterov ◽  
Matthias Staufenbiel ◽  
Darren Wolfe ◽  
Shaohua Huang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Amyloid Β ◽  
Liver X Receptor ◽  
Receptor Ligand ◽  
Model Of Alzheimer’S Disease

scholarly journals Molecular Patterns of Neurodevelopmental Preconditioning: A Study of the Effects of Antenatal Steroid Therapy in a Protein-Restriction Mouse Model

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Clarissa Velayo ◽  
Takuya Ito ◽  
Yupeng Dong ◽  
Miyuki Endo ◽  
Rika Sugibayashi ◽  
...  
Keyword(s):  
Mouse Model ◽  
Microarray Analysis ◽  
Steroid Therapy ◽  
Regulatory Networks ◽  
Harmful Effect ◽  
High Stress ◽  
Protein Restriction ◽  
Late Gestation ◽  
Treatment Protocols ◽  
Antenatal Steroid

Introduction. Prenatal programming secondary to maternal protein restriction renders an inherent susceptibility to neural compromise in neonates and any addition of glucocorticosteroids results in further damage. This is an investigation of consequent global gene activity due to effects of antenatal steroid therapy on a protein restriction mouse model. Methods. C57BL/6N pregnant mice were administered control or protein restricted diets and subjected to either 100 μg/Kg of dexamethasone sodium phosphate with normosaline or normosaline alone during late gestation (E10–E17). Nontreatment groups were also included. Brain samples were collected on embryonic day 17 and analyzed by mRNA microarray analysis. Results. Microarray analyses presented 332 significantly regulated genes. Overall, neurodevelopmental genes were overrepresented and a subset of 8 genes allowed treatment segregation through the hierarchical clustering method. The addition of stress or steroids greatly affected gene regulation through glucocorticoid receptor and stress signaling pathways. Furthermore, differences between dexamethasone-administered treatments implied a harmful effect during conditions of high stress. Microarray analysis was validated using qPCR. Conclusion. The effects of antenatal steroid therapy vary in fetuses according to maternal-fetal factors and environmental stimuli. Defining the key regulatory networks that signal either beneficial or damaging corticosteroid action would result in valuable adjustments to current treatment protocols.

scholarly journals Stimulation of Liver X Receptor Has Potent Anti-HIV Effects in a Humanized Mouse Model of HIV Infection

2015 ◽  
Vol 354 (3) ◽  
pp. 376-383 ◽  
Author(s):  
Ali Ramezani ◽  
Larisa Dubrovsky ◽  
Tatiana Pushkarsky ◽  
Dmitri Sviridov ◽  
Sara Karandish ◽  
...  
Keyword(s):  
Mouse Model ◽  
Hiv Infection ◽  
Liver X Receptor ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Anti Hiv ◽  
Stimulation Of

scholarly journals Cross-talk between Thyroid Hormone Receptor and Liver X Receptor Regulatory Pathways Is Revealed in a Thyroid Hormone Resistance Mouse Model

2005 ◽  
Vol 281 (1) ◽  
pp. 295-302 ◽  
Author(s):  
Koshi Hashimoto ◽  
Ronald N. Cohen ◽  
Masanobu Yamada ◽  
Kathleen R. Markan ◽  
Tsuyoshi Monden ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Mouse Model ◽  
Cross Talk ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Liver X Receptor ◽  
Hormone Resistance ◽  
Regulatory Pathways ◽  
Thyroid Hormone Resistance
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