Adamtsl2 deletion results in bronchial fibrillin microfibril accumulation and bronchial epithelial dysplasia--a novel mouse model providing insights into geleophysic dysplasia

Disease Models & Mechanisms
Dirk HubmacherSuneel S Apte

Abstract

Mutations in the secreted glycoprotein ADAMTSL2 cause recessive geleophysic dysplasia (GD) in humans and Musladin-Lueke syndrome (MLS) in dogs. GD is a severe, often lethal, condition presenting with short stature, brachydactyly, stiff skin, joint contractures, tracheal-bronchial stenosis and cardiac valve anomalies, whereas MLS is non-lethal and characterized by short stature and severe skin fibrosis. Although most mutations in fibrillin-1 (FBN1) cause Marfan syndrome (MFS), a microfibril disorder leading to transforming growth factor-β (TGFβ) dysregulation, domain-specific FBN1 mutations result in dominant GD. ADAMTSL2 has been previously shown to bind FBN1 and latent TGFβ-binding protein-1 (LTBP1). Here, we investigated mice with targeted Adamtsl2 inactivation as a new model for GD (Adamtsl2(-/-) mice). An intragenic lacZ reporter in these mice showed that ADAMTSL2 was produced exclusively by bronchial smooth muscle cells during embryonic lung development. Adamtsl2(-/-) mice, which died at birth, had severe bronchial epithelial dysplasia with abnormal glycogen-rich inclusions in bronchial epithelium resembling the cellular anomalies described previously in GD. An increase in microfibrils in the bronchial wall was associated ...Continue Reading

References

Apr 1, 1991·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·D R KeeneR W Glanville
Nov 1, 1984·American Journal of Medical Genetics·J SprangerJ M Opitz
Jan 1, 1995·Archives of Ophthalmology·H M WheatleyJ A Whittum-Hudson
Aug 1, 1996·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·J TaipaleJ Keski-Oja
Dec 5, 2000·Matrix Biology : Journal of the International Society for Matrix Biology·F SegadeR P Mecham
Jul 20, 2001·The Journal of Biological Chemistry·K TiedemannD P Reinhardt
Jul 27, 2001·The Journal of Cell Biology·E Arteaga-SolisF Ramirez
Aug 2, 2001·The Journal of Biological Chemistry·S A JensenA S Weiss
Jan 18, 2002·The Journal of Biological Chemistry·Fernando SegadeRobert P Mecham
Oct 26, 2002·The Journal of Biological Chemistry·Guoqing LinDieter P Reinhardt
Feb 25, 2003·Nature Genetics·Enid R NeptuneHarry C Dietz
Mar 27, 2004·The Journal of Biological Chemistry·Claudio C WerneckRobert P Mecham
Dec 22, 2005·Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology·P PanagopoulosA Antsaklis
Jan 13, 2006·The Journal of Biological Chemistry·Luca CartaFrancesco Ramirez
Mar 31, 2006·Journal of Medical Genetics·P N RobinsonM Godfrey
Apr 3, 2007·American Journal of Physiology. Lung Cellular and Molecular Physiology·Hidehiko NakanishiJesse D Roberts
May 19, 2007·Matrix Biology : Journal of the International Society for Matrix Biology·Bon-Hun KooSuneel S Apte
Nov 17, 2007·American Journal of Respiratory Cell and Molecular Biology·Stephen E McGowanTimothy M Ritty
Mar 15, 2008·The Journal of Biological Chemistry·Gerhard SengleLynn Y Sakai
May 31, 2008·Annals of Tropical Paediatrics·Ozlem GirayDuygu Gürel
Jun 27, 2008·The New England Journal of Medicine·Benjamin S BrookeHarry C Dietz
Jul 16, 2008·The Journal of Biological Chemistry·Justin S WeinbaumRobert P Mecham
Jul 26, 2008·Journal of Cell Science·Rachel KinseyCay M Kielty
Nov 28, 2008·Molecular Biology of the Cell·Laetitia SabatierDieter P Reinhardt
Jul 25, 2009·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·Nele Pentsuk, Jan Willem van der Laan
Aug 12, 2010·Journal of Cell Science·Teresa Massam-WuCay M Kielty
Sep 22, 2010·The Journal of Cell Biology·Harikiran NistalaFrancesco Ramirez
Mar 19, 2011·Journal of Medical Genetics·Slimane AllaliValérie Cormier-Daire
Jun 21, 2011·American Journal of Human Genetics·Carine Le GoffValérie Cormier-Daire

❮ Previous
Next ❯

Citations

Apr 14, 2016·Journal of Medical Genetics·Aideen M McInerney-LeoValerie Cormier-Daire
Feb 6, 2017·Journal of Veterinary Internal Medicine·R A PackerG D Shelton
Jul 31, 2018·Human Molecular Genetics·Ewa J MularczykClair Baldock
Oct 12, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Laure DelhonCarine Le Goff
Dec 24, 2018·The European Respiratory Journal·Wenguang YinDidier Y R Stainier
Sep 15, 2017·International Journal of Experimental Pathology·Cay M Kielty
Oct 4, 2017·American Journal of Physiology. Lung Cellular and Molecular Physiology·David E Surate SolaligueRory E Morty
Sep 3, 2020·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Brandon Satz-Jacobowitz, Dirk Hubmacher
Jun 16, 2019·Cellular and Molecular Life Sciences : CMLS·Takeshi OichiTaku Saito
Jun 27, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Lasse D JensenJulianna Kele
Sep 12, 2020·The Journal of Biological Chemistry·Ao ZhangRobert S Haltiwanger
Sep 16, 2020·The Journal of Biological Chemistry·Semeli PlatsakiPascale Marchot
Sep 4, 2020·Annals of the New York Academy of Sciences·Sarah StanleyDirk Hubmacher
Aug 24, 2021·Investigative Ophthalmology & Visual Science·Hang-Jing WuJohn Kuchtey

❮ Previous
Next ❯

Datasets Mentioned

BETA
GM-130

Methods Mentioned

BETA
electron microscopy
biopsies
genotyping
PCR
periodic acid Schiff
transmission electron microscopy
surface plasmon resonance
light microscopy
chip

Software Mentioned

Origin
OriginLab
ImageJ
PrimerQuest Design Tool

Related Concepts

Related Feeds

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.