Mouse models of hereditary hemorrhagic telangiectasia: recent advances and future challenges

Frontiers in Genetics
Simon Tual-ChalotHelen M Arthur

Abstract

Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder characterized by a multi-systemic vascular dysplasia and hemorrhage. The precise factors leading to these vascular malformations are not yet understood and robust animal models of HHT are essential to gain a detailed understanding of the molecular and cellular events that lead to clinical symptoms, as well as to test new therapeutic modalities. Most cases of HHT are caused by mutations in either endoglin (ENG) or activin receptor-like kinase 1 (ACVRL1, also known as ALK1). Both genes are associated with TGFβ/BMP signaling, and loss of function mutations in the co-receptor ENG are causal in HHT1, while HHT2 is associated with mutations in the signaling receptor ACVRL1. Significant advances in mouse genetics have provided powerful ways to study the function of Eng and Acvrl1 in vivo, and to generate mouse models of HHT disease. Mice that are null for either Acvrl1 or Eng genes show embryonic lethality due to major defects in angiogenesis and heart development. However mice that are heterozygous for mutations in either of these genes develop to adulthood with no effect on survival. Although these heterozygous mice exhibit selected vascular phenotypes relevant to the...Continue Reading

References

Oct 1, 1990·The Journal of Investigative Dermatology·I M BravermanB S Jacobson
May 29, 1999·Science·D Y LiD P Wendel
Nov 24, 1999·The Journal of Clinical Investigation·A BourdeauM Letarte
Mar 16, 2000·Proceedings of the National Academy of Sciences of the United States of America·S P OhE Li
Feb 18, 2003·Human Molecular Genetics·Sudha SrinivasanDouglas A Marchuk
Jan 30, 2004·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Bin XuGuo-Yuan Yang
Sep 24, 2004·The EMBO Journal·Franck LebrinPeter ten Dijke
Sep 13, 2005·Journal of Medical Genetics·T G W LetteboerC J J Westermann
Jan 13, 2006·Cardiovascular Research·Mirjana JerkicJosé M López-Novoa
Jun 6, 2006·Nature Medicine·Shivalingappa VenkateshaS Ananth Karumanchi
Nov 8, 2006·Circulation·Linda W van LaakeChristine L Mummery
Jan 17, 2007·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Gaëtan LescaUNKNOWN French-Italian-Rendu-Osler Network
Feb 27, 2007·Angiogenesis·Marcus Fruttiger
May 17, 2007·Genesis : the Journal of Genetics and Development·Kathleen R AllinsonHelen M Arthur
Aug 3, 2007·Human Molecular Genetics·Pascal Brouillard, Miikka Vikkula
Mar 20, 2009·Human Molecular Genetics·Nisha LimayeMiikka Vikkula
Aug 12, 2009·Annals of Neurology·Yongmei ChenWilliam L Young
Mar 13, 2010·Circulation Research·Marwa MahmoudHelen M Arthur
Apr 29, 2010·Cancer Research·Lukas J A C HawinkelsPeter ten Dijke
Jul 20, 2010·Translational Stroke Research·Qi HaoWilliam L Young
Sep 18, 2010·Inflammatory Bowel Diseases·Mirjana JerkicMichelle Letarte
Mar 26, 2011·Annals of Neurology·Espen J WalkerWilliam L Young
Feb 14, 2012·Stroke; a Journal of Cerebral Circulation·Ian MiltonTsugio Seki
Mar 17, 2012·Developmental Cell·Bruno LarrivéeAnne Eichmann
May 10, 2012·Stroke; a Journal of Cerebral Circulation·Espen J WalkerWilliam L Young
Dec 18, 2012·Arteriosclerosis, Thrombosis, and Vascular Biology·Wanqiu ChenWilliam L Young

❮ Previous
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Citations

Jan 29, 2016·Thrombosis and Haemostasis·Roberto ZarrabeitiaLuisa M Botella
Mar 29, 2016·World Neurosurgery·Michael KarsyWilliam T Couldwell
Sep 21, 2016·The Journal of Cell Biology·Nicolas BaeyensMartin A Schwartz
Mar 25, 2016·PLoS Genetics·Luisa Ojeda-FernándezLuisa M Botella
Jun 1, 2017·Nature Cell Biology·Victoria L Bautch
Feb 14, 2018·Current Opinion in Hematology·Wade W Sugden, Arndt F Siekmann
Apr 21, 2018·Science·Martin A SchwartzMichael Simons
Aug 11, 2017·Expert Opinion on Therapeutic Targets·Lidia Ruiz-LlorenteCarmelo Bernabeu
Oct 1, 2017·Circulation Research·Sara I CunhaMaria Grazia Lampugnani
Jan 30, 2016·Arteriosclerosis, Thrombosis, and Vascular Biology·Konstantinos GkatzisFranck Lebrin
Sep 25, 2018·The Journal of Pathology·Maria Catalina Gomez-PuertoGonzalo Sanchez-Duffhues
Feb 26, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Kristy Red-Horse, Arndt F Siekmann
Nov 7, 2019·The Journal of Clinical Investigation·Santiago RuizPhilippe Marambaud
Apr 25, 2018·HNO·F Haubner, T Kühnel
Nov 20, 2016·The Journal of Pathology·Sarah E Wetzel-StrongDouglas A Marchuk
Dec 13, 2016·Angiogenesis·Elena Núñez-GómezJosé M López-Novoa
Aug 15, 2020·Frontiers in Physiology·Kazuhide S Okuda, Benjamin M Hogan
Mar 27, 2020·Biomolecules·Andreas BennAn Zwijsen
Jun 19, 2015·Veterinary Sciences·Jude Amal Raj, Marcus Stoodley
Feb 23, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Hanna M PeacockElizabeth A V Jones
Nov 17, 2019·International Journal of Molecular Sciences·Leandro Barbosa Do PradoHua Su
Jun 9, 2020·Angiogenesis·Esha SinghHelen M Arthur
Oct 22, 2020·Journal of Clinical Medicine·Anthony CannavicciMichael J B Kutryk
Nov 11, 2020·Journal of Clinical Medicine·Carmelo BernabeuMichelle Letarte
Oct 22, 2019·American Journal of Human Genetics·Daniel A SnellingsDouglas A Marchuk
Mar 27, 2021·Current Opinion in Hematology·Ondine Cleaver

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Methods Mentioned

BETA
transgenic

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