Conditional disruption of the peroxisome proliferator-activated receptor gamma gene in mice results in lowered expression of ABCA1, ABCG1, and apoE in macrophages and reduced cholesterol efflux.

Molecular and Cellular Biology
Taro E AkiyamaFrank J Gonzalez

Abstract

Disruption of the peroxisome proliferator-activated receptor gamma (PPAR gamma) gene causes embryonic lethality due to placental dysfunction. To circumvent this, a PPAR gamma conditional gene knockout mouse was produced by using the Cre-loxP system. The targeted allele, containing loxP sites flanking exon 2 of the PPAR gamma gene, was crossed into a transgenic mouse line expressing Cre recombinase under the control of the alpha/beta interferon-inducible (MX) promoter. Induction of the MX promoter by pIpC resulted in nearly complete deletion of the targeted exon, a corresponding loss of full-length PPAR gamma mRNA transcript and protein, and marked reductions in basal and troglitazone-stimulated expression of the genes encoding lipoprotein lipase, CD36, LXR alpha, and ABCG1 in thioglycolate-elicited peritoneal macrophages. Reductions in the basal levels of apolipoprotein E (apoE) mRNA in macrophages and apoE protein in total plasma and high-density lipoprotein (HDL) were also observed in pIpC-treated PPAR gamma-MXCre(+) mice. Basal cholesterol efflux from cholesterol-loaded macrophages to HDL was significantly reduced after disruption of the PPAR gamma gene. Troglitazone selectively inhibited ABCA1 expression (while rosiglitazon...Continue Reading

References

Dec 1, 1986·Molecular and Cellular Biology·P StaeheliJ G Sutcliffe
Mar 27, 1987·Science·K L WionR M Lawn
Aug 1, 1995·The Journal of Clinical Investigation·W A BoisvertL K Curtiss
Sep 8, 1995·Science·R KühnK Rajewsky
Sep 17, 1994·Lancet·J L Witztum
Aug 1, 1994·The Journal of Experimental Medicine·W J de VilliersS Gordon
Oct 29, 1993·Biochemical and Biophysical Research Communications·F ChenB W O'Malley
Apr 15, 1996·Genes & Development·R P BrunB M Spiegelman
Jun 11, 1996·Proceedings of the National Academy of Sciences of the United States of America·M LaksoH Westphal
Aug 1, 1996·Arteriosclerosis, Thrombosis, and Vascular Biology·L M YesnerR L Silverstein
Jun 1, 1996·Atherosclerosis·N NoguchiT Kodama
Oct 15, 1996·The Journal of Clinical Investigation·R E LawW A Hsueh
Jan 7, 1997·Proceedings of the National Academy of Sciences of the United States of America·P TontonozB M Spiegelman
Apr 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·B M FormanR M Evans
Apr 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·S A KliewerJ M Lehmann
Apr 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·S FazioM F Linton
Feb 1, 1997·Biochimie·B M SpiegelmanR Brun
Mar 20, 1998·The Journal of Clinical Endocrinology and Metabolism·J MinamikawaH Koshiyama
Jul 14, 1998·Molecular Cell·E MuellerB M Spiegelman
Oct 22, 1998·La Revue du praticien·P Giral
Jun 22, 1999·The Journal of Clinical Investigation·V R BabaevM F Linton

❮ Previous
Next ❯

Citations

Sep 20, 2006·Pflügers Archiv : European journal of physiology·Hiroyuki Kusuhara, Yuichi Sugiyama
Apr 18, 2013·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Chao HeXiao-Mei Guo
Jun 7, 2005·The Journal of Nutritional Biochemistry·Marie-Louise RickettsNeil F Shay
Jun 14, 2005·Molecular Immunology·Michelle B CrosbyTamara K Nowling
Sep 6, 2003·Atherosclerosis·Y Stein, O Stein
May 17, 2003·Prostaglandins & Other Lipid Mediators·David Bishop-Bailey, Jessica Wray
Sep 6, 2003·International Journal of Cardiology·Paolo PudduAntonio Muscari
Dec 9, 2003·International Journal of Cardiology·Dao-Quan PengJiang Li
Jun 6, 2003·Current Opinion in Genetics & Development·Roger D Cox, Steve D M Brown
Jun 5, 2003·Biochimica Et Biophysica Acta·Jeffrey M PetersFrank J Gonzalez
Apr 12, 2003·Current Opinion in Pharmacology·Gordon A FrancisJohan Auwerx
Sep 12, 2002·Trends in Molecular Medicine·Caroline DuvalBart Staels
Oct 18, 2002·Trends in Molecular Medicine·Gordon A FrancisJohan Auwerx
Sep 28, 2002·International Immunopharmacology·Xia Zhang, Howard A Young
Jul 23, 2009·The British Journal of Nutrition·Robert Ringseis, Klaus Eder
Jul 9, 2011·The British Journal of Nutrition·Josep Bassaganya-RieraRaquel Hontecillas
Mar 1, 2012·International Journal of Obesity : Journal of the International Association for the Study of Obesity·J Laurencikiene, M Rydén
Mar 2, 2005·Nature Reviews. Drug Discovery·Patrick Linsel-Nitschke, Alan R Tall
Sep 25, 2009·The Journal of Biological Chemistry·Xinbing HanWilliam A Boisvert
Sep 1, 2009·The Journal of Biological Chemistry·Haibiao GongWen Xie
Oct 20, 2010·The Journal of Biological Chemistry·Michael Schupp, Mitchell A Lazar
Dec 9, 2008·Antioxidants & Redox Signaling·Milton HamblinY Eugene Chen
May 15, 2012·Carcinogenesis·Graham Skelhorne-GrossChristopher J B Nicol
Oct 5, 2010·Cardiovascular Research·Söhnke HinrichsKlaus-Dieter Schlüter
Jun 5, 2002·Current Opinion in Lipidology·Günter W Klappacher, Christopher K Glass
Sep 9, 2005·Current Opinion in Lipidology·Liza Makowski, Gökhan S Hotamisligil
May 9, 2006·Current Opinion in Lipidology·Angel BaldánPeter A Edwards
Feb 3, 2005·Genes & Development·Stavit DroriBruce M Spiegelman
Feb 5, 2011·Clinical and Experimental Pharmacology & Physiology·Wei PangYi Zhu
Apr 17, 2009·The Journal of Pharmacology and Experimental Therapeutics·Rajani KaimalRuitang Deng
Jun 4, 2008·Annual Review of Biochemistry·Peter Tontonoz, Bruce M Spiegelman
Oct 12, 2004·Annual Review of Cell and Developmental Biology·Antonio Castrillo, Peter Tontonoz
Jul 20, 2006·Annual Review of Nutrition·Kevin Fritsche
Jan 9, 2003·Annual Review of Physiology·Gordon A FrancisJohan Auwerx
Nov 11, 2006·American Journal of Physiology. Gastrointestinal and Liver Physiology·Yatrik M ShahFrank J Gonzalez
Mar 1, 2008·PPAR Research·Cadence E MingeRobert J Norman

❮ Previous
Next ❯

Related Concepts

Related Feeds

ApoE, Lipids & Cholesterol

Serum cholesterol, triglycerides, apolipoprotein B (APOB)-containing lipoproteins (very low-density lipoprotein (VLDL), immediate-density lipoprotein (IDL), and low-density lipoprotein (LDL), lipoprotein A (LPA)) and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are all connected in diseases. Here is the latest research.

ApoE Phenotypes

Apolipoprotein E (APOE) is a protein involved in fat metabolism and associated with the pathogenesis of Alzheimer's disease and cardiovascular disease. Here is the latest research on APOE phenotypes.