Abstract
We have generated a mouse that cannot synthesize very long acyl chain (C22-C24) ceramides (Pewzner-Jung, Y., Park, H., Laviad, E. L., Silva, L. C., Lahiri, S., Stiban, J., Erez-Roman, R., Brugger, B., Sachsenheimer, T., Wieland, F. T., Prieto, M., Merrill, A. H., and Futerman, A. H. (2010) J. Biol. Chem. 285, 10902-10910) due to ablation of ceramide synthase 2 (CerS2). As a result, significant changes were observed in the sphingolipid profile of livers from these mice, including elevated C16-ceramide and sphinganine levels. We now examine the functional consequences of these changes. CerS2 null mice develop severe nonzonal hepatopathy from about 30 days of age, the age at which CerS2 expression peaks in wild type mice, and display increased rates of hepatocyte apoptosis and proliferation. In older mice there is extensive and pronounced hepatocellular anisocytosis with widespread formation of nodules of regenerative hepatocellular hyperplasia. Progressive hepatomegaly and noninvasive hepatocellular carcinoma are also seen from approximately 10 months of age. Even though CerS2 is found at equally high mRNA levels in kidney and liver, there are no changes in renal function and no pathological changes in the kidney. High throughput...Continue Reading
References
Dec 16, 1993·Nature·Y XiongD Beach
Mar 1, 1997·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J H AlbrechtM Y Hu
Oct 23, 1997·Genome Research·S Audic, J M Claverie
Feb 17, 1998·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·G S BondyM G Barker
Sep 16, 1998·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·J R Ciacci-ZanellaC Jones
Sep 16, 1998·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·D E AmacherJ E Burkhardt
Aug 4, 1999·Proceedings of the National Academy of Sciences of the United States of America·T YamashitaR L Proia
Oct 16, 1999·The Journal of Biological Chemistry·R L ThomasA A Amoscato
Dec 11, 1999·Nucleic Acids Research·M Kanehisa, S Goto
Apr 11, 2001·Toxicological Sciences : an Official Journal of the Society of Toxicology·Y P DraganK A Voss
May 22, 2001·Environmental Health Perspectives·K A VossJ K Porter
Dec 26, 2001·Science's STKE : Signal Transduction Knowledge Environment·M C Sullards, A H Merrill
Jun 19, 2002·Biochimica Et Biophysica Acta·Robert C Dickson, Robert L Lester
Nov 14, 2002·Cell Cycle·Neil D Perkins
Aug 13, 2003·The Journal of Biological Chemistry·Christian RiebelingAnthony H Futerman
Aug 22, 2003·Nature·Nika N DanialStanley J Korsmeyer
Dec 25, 2003·Toxicologic Pathology·Peter Bannasch
Jun 1, 1996·Trends in Cell Biology·A H MerrillR T Riley
Aug 20, 2004·The Journal of Biological Chemistry·Serap KoybasiBesim Ogretmen
Apr 5, 2005·Toxicologic Pathology·James R HaileyAbraham Nyska
May 17, 2005·Methods : a Companion to Methods in Enzymology·Alfred H MerrillElaine Wang
Jun 28, 2005·Nucleic Acids Research·Bing ZhangJay Snoddy
Oct 12, 2005·Biochimica Et Biophysica Acta·Mohammad Reza HojjatiXian-Cheng Jiang
Dec 31, 2005·Nucleic Acids Research·Minoru KanehisaMika Hirakawa
Apr 15, 2006·Toxicological Sciences : an Official Journal of the Society of Toxicology·Ronald T Riley, Kenneth A Voss
Apr 19, 2006·Cancer Research·Mark KatzenellenbogenDaniel Goldenberg
Jun 24, 2006·The Journal of Biological Chemistry·Yael Pewzner-JungAnthony H Futerman
Feb 20, 2007·Molecular Cancer Therapeutics·Can E SenkalBesim Ogretmen
Mar 7, 2007·Cell Metabolism·William L HollandScott A Summers
Jul 4, 2007·Nutrition Reviews·William L HollandScott A Summers
Aug 19, 2007·Molecular Cancer Research : MCR·Junxia MinStephen Alexander
Aug 25, 2007·Diabetes·Grace FlockDaniel J Drucker
Dec 14, 2007·Nucleic Acids Research·Minoru KanehisaYoshihiro Yamanishi
Jan 1, 2008·The Journal of Biological Chemistry·Elad L LaviadAnthony H Futerman
Apr 3, 2008·Physiological Genomics·Matthew T FlowersAlan D Attie
Apr 11, 2008·Prostaglandins & Other Lipid Mediators·Shoghag PanjarianGhassan S Dbaibo
May 31, 2008·Bioinformatics·Sebastian BauerPeter N Robinson
Aug 5, 2008·The Journal of Biological Chemistry·Junfei JinYi-Te Hsu
Aug 30, 2008·Sub-cellular Biochemistry·Sahar A SaddoughiBesim Ogretmen
Oct 4, 2008·Science·Xinzhu DengRichard Kolesnick
Oct 18, 2008·BMC Genomics·Tim HulsenWynand Alkema
Nov 19, 2008·Glycoconjugate Journal·Sandro SonninoKazuhisa Iwabuchi
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
Jan 14, 2009·The Journal of Cell Biology·Xin WangJairaj K Acharya
Mar 13, 2009·Carcinogenesis·Susanne SchiffmannSabine Grösch
Apr 18, 2009·Science·Vincent MenuzJean-Claude Martinou
Jun 2, 2009·Molecular Pharmacology·Teneille WalkerPaul Dent
Sep 5, 2009·The Biochemical Journal·Stefka D SpassievaLina M Obeid
Sep 5, 2009·The Journal of Clinical Investigation·Nicolas LeuenbergerWalter Wahli
Oct 6, 2009·The Journal of Biological Chemistry·Silke ImgrundKlaus Willecke
Citations
Apr 18, 2013·Histochemistry and Cell Biology·Christiane KremserKlaus Willecke
Jan 17, 2012·Neurochemical Research·Erhard Bieberich
Nov 23, 2013·Cell Death & Disease·M AliA H Futerman
Dec 14, 2012·Nature Reviews. Cancer·Samy A F Morad, Myles C Cabot
Jun 28, 2011·The Journal of Biological Chemistry·Oshrit Ben-DavidAnthony H Futerman
Apr 12, 2012·The Journal of Biological Chemistry·Su-Yeon LeeTae-Sik Park
Jan 4, 2013·The Journal of Biological Chemistry·Hila ZigdonAnthony H Futerman
Apr 2, 2011·Cold Spring Harbor Perspectives in Biology·J Thomas HannichHoward Riezman
Apr 15, 2011·Journal of Lipids·Erhard Bieberich
Jan 11, 2012·Journal of Lipid Research·Liana C SilvaAnthony H Futerman
Jan 5, 2012·PloS One·Julia RanzingerVedat Schwenger
Nov 11, 2010·Future Oncology·Suriyan PonnusamyBesim Ogretmen
Apr 8, 2011·World Journal of Gastroenterology : WJG·Marek HartlebPiotr Milkiewicz
Jun 28, 2014·Biomolecules·Anthony S DonTimothy A Couttas
Aug 28, 2014·Reproduction : the Official Journal of the Society for the Study of Fertility·Luis Manuel Baldoceda-BaldeonClaude Robert
Sep 23, 2014·Biochimica Et Biophysica Acta·Woo-Jae ParkAnthony H Futerman
Oct 13, 2010·Proceedings of the National Academy of Sciences of the United States of America·Yusuke OhnoAkio Kihara
Mar 10, 2015·International Journal of Molecular Sciences·Norishi Ueda
Jul 18, 2015·FEBS Letters·Mohammad AliAnthony H Futerman
Nov 5, 2013·Biochimica Et Biophysica Acta·Heike Schulze, Konrad Sandhoff
Sep 12, 2013·Biochimica Et Biophysica Acta·Joo-Won ParkAnthony H Futerman
Jan 11, 2012·The International Journal of Biochemistry & Cell Biology·Daniela HartmannSabine Grösch
Dec 3, 2011·Progress in Lipid Research·Sabine GröschGerd Geisslinger
Jul 19, 2011·Trends in Cell Biology·Shweta AggarwalMikael Simons
Nov 3, 2010·Advances in Enzyme Regulation·Linda A Heffernan-Stroud, Lina M Obeid
Aug 23, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Joo-Won ParkAnthony H Futerman
Feb 26, 2013·The FEBS Journal·Ursula Loizides-Mangold
Oct 31, 2014·Annals of Clinical and Translational Neurology·Mai-Britt MosbechNils J Færgeman
Mar 12, 2010·IUBMB Life·Michal Levy, Anthony H Futerman
Oct 29, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Georgios GrammatikosJosef Pfeilschifter
Oct 9, 2014·Cell Metabolism·Suryaprakash RaichurScott A Summers
Sep 26, 2015·Lipids·Lin MaBertram Y Fong
Oct 5, 2014·Journal of Hepatology·Carmen Garcia-RuizJosé C Fernández-Checa
Jan 31, 2015·Biochimica Et Biophysica Acta·Mohammed Dany, Besim Ogretmen
Aug 25, 2015·Nature Medicine·Anna CantalupoAnnarita Di Lorenzo
Aug 27, 2014·Archives of Toxicology·Nicolas LoiseauIsabelle P Oswald
Jan 18, 2012·The Biochemical Journal·Thomas D MullenLina M Obeid
Oct 7, 2014·Biochimica Et Biophysica Acta·S Rodriguez-CuencaA Vidal-Puig
Oct 26, 2010·Progress in Lipid Research·Gauri A Patwardhan, Yong-Yu Liu
Jun 27, 2015·Endocrine-related Cancer·Woo-Jae ParkAnthony H Futerman
Jul 26, 2015·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Florina RegeleRainer Oberbauer
Feb 11, 2015·Biochimica Et Biophysica Acta·Frédérique SabourdyThierry Levade
Jul 31, 2012·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Genevieve BondyRonald T Riley
May 15, 2012·Biochimica Et Biophysica Acta·Takayuki SassaAkio Kihara
Jun 26, 2013·The International Journal of Biochemistry & Cell Biology·Susanne SchiffmannSabine Grösch
Aug 13, 2013·Biochimie·Aviram Kogot-Levin, Ann Saada
Apr 25, 2013·Biochimica Et Biophysica Acta·Rotem Tidhar, Anthony H Futerman
Feb 1, 2015·Apoptosis : an International Journal on Programmed Cell Death·Carmen Garcia-RuizJosé C Fernández-Checa
Jan 21, 2012·Biophysical Journal·Larisa YurlovaMikael Simons
Jan 27, 2015·Journal of Bioenergetics and Biomembranes·Gauri A PatwardhanLeah J Siskind