Loss of Mpdz impairs ependymal cell integrity leading to perinatal-onset hydrocephalus in mice

EMBO Molecular Medicine
Anja FeldnerAndreas Fischer

Abstract

Hydrocephalus is a common congenital anomaly. LCAM1 and MPDZ (MUPP1) are the only known human gene loci associated with non-syndromic hydrocephalus. To investigate functions of the tight junction-associated protein Mpdz, we generated mouse models. Global Mpdz gene deletion or conditional inactivation in Nestin-positive cells led to formation of supratentorial hydrocephalus in the early postnatal period. Blood vessels, epithelial cells of the choroid plexus, and cilia on ependymal cells, which line the ventricular system, remained morphologically intact in Mpdz-deficient brains. However, flow of cerebrospinal fluid through the cerebral aqueduct was blocked from postnatal day 3 onward. Silencing of Mpdz expression in cultured epithelial cells impaired barrier integrity, and loss of Mpdz in astrocytes increased RhoA activity. In Mpdz-deficient mice, ependymal cells had morphologically normal tight junctions, but expression of the interacting planar cell polarity protein Pals1 was diminished and barrier integrity got progressively lost. Ependymal denudation was accompanied by reactive astrogliosis leading to aqueductal stenosis. This work provides a relevant hydrocephalus mouse model and demonstrates that Mpdz is essential to maint...Continue Reading

References

Jan 1, 1995·Journal of Neuropathology and Experimental Neurology·H B Sarnat
Apr 16, 1998·FEBS Letters·C UllmerH Lübbert
Jun 13, 1998·European Journal of Pediatrics·C Schrander-Stumpel, J P Fryns
Sep 14, 1999·Brain Research Bulletin·J W Fawcett, R A Asher
Dec 5, 2000·Molecular Biology of the Cell·M SaitouS Tsukita
Feb 13, 2001·Brain Research·B RolfU Bartsch
May 16, 2001·Genesis : the Journal of Genetics and Development·R ConstienB Arnold
Apr 23, 2003·Brain Research·B SitekH Luebbert
Apr 30, 2003·Human Molecular Genetics·Brian E Davy, Michael L Robinson
May 14, 2003·The Journal of Cell Biology·Takehiro NittaShoichiro Tsukita
Apr 13, 2007·Molecular Biology of the Cell·Xuefei MaRobert S Adelstein
Aug 31, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Malik KhelfaouiPierre Billuart
Sep 4, 2007·Developmental Cell·Tamilla NechiporukValeri Vasioukhin
Nov 17, 2007·Biochimica Et Biophysica Acta·Emeline AssématDominique Massey-Harroche
Feb 6, 2008·The Journal of Cell Biology·Karl-Ferdinand LechtreckGeorge B Witman
Jun 10, 2008·Journal of Neurochemistry·Marcel A EstévezJay M Baraban
Jul 25, 2008·PLoS Biology·Konstantinos MeletisJonas Frisén
Mar 4, 2009·Molecular and Cellular Biology·Makoto AdachiShoichiro Tsukita
May 5, 2009·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·Ester GarneHelen Dolk
Oct 16, 2009·Molecular Biology of the Cell·Marouan AbouhamedMartin Bähler
Dec 25, 2009·Acta Neuropathologica·Hartwig Wolburg, Werner Paulus
Mar 9, 2011·Neuron·Maria K LehtinenChristopher A Walsh
May 6, 2011·The Journal of Biological Chemistry·Chuanshen WuArie Horowitz
Sep 20, 2011·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Giuseppe CinalliEmilio Cianciulli
Dec 15, 2012·Journal of Medical Genetics·Mohammed S Al-DosariFowzan S Alkuraya
Dec 21, 2012·The Journal of Cell Biology·Siu P NgokPanos Z Anastasiadis
Jun 28, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Fabien BinaméJacqueline Trotter
Jul 25, 2013·Experimental Cell Research·Emeline AssématDominique Massey-Harroche
Mar 14, 2014·Journal of the Royal Society, Interface·Bercan SiyahhanVartan Kurtcuoglu
Jun 17, 2014·European Journal of Medical Genetics·Hannah M Tully, William B Dobyns
Jul 22, 2014·Tissue Barriers·Antonio J JiménezJosé-Manuel Pérez-Fígares

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Citations

Apr 6, 2018·ELife·Fabian TetzlaffAndreas Fischer
Feb 3, 2018·Fluids and Barriers of the CNS·Richard F KeepLester R Drewes
Jul 4, 2019·Molecular Biology of the Cell·Arthur Marivin, Mikel Garcia-Marcos
Dec 7, 2018·EMBO Molecular Medicine·Junning YangArie Horowitz
Aug 7, 2019·Disease Models & Mechanisms·Francesco ChianiGlauco P Tocchini-Valentini
Jun 20, 2019·Frontiers in Cellular Neuroscience·Janne HakanenFadel Tissir
Apr 27, 2018·Cellular and Molecular Life Sciences : CMLS·Sophie M HapakSourav Ghosh
Jul 23, 2018·Journal of Neuropathology and Experimental Neurology·Leandro Castaneyra-RuizDavid D Limbrick
Mar 15, 2019·Journal of the American Society of Nephrology : JASN·Michael IgnarskiRoman-Ulrich Müller
May 1, 2021·Neuroscience and Biobehavioral Reviews·Inge C M VerheggenWalter H Backes
Jul 8, 2021·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Adam J KundishoraKristopher T Kahle
Jul 9, 2021·Fluids and Barriers of the CNS·Vijay KumarJaebong Kim
Jul 16, 2021·Journal of Applied Physiology·Jeff F Dunn, Albert M Isaacs
Sep 3, 2021·Neuropsychiatric Disease and Treatment·Wen-Jie WangZixiao Li

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Methods Mentioned

BETA
electron microscopy
transgenic
transfection
gene trap
transfections
Assay

Software Mentioned

Osirix Imaging
ZEN Blue
Fiji
xls
Mendel

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