DOCSLIB.ORG

Distribution of Type IV Collagen in the Cochlea in Alport Syndrome

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Distribution of Type IV Collagen in the Cochlea in Alport Syndrome ORIGINAL ARTICLE Distribution of Type IV Collagen in the Cochlea in Alport Syndrome Andreas F. Zehnder, MD; Joe C. Adams, PhD; Peter A. Santi, PhD; Arthur G. Kristiansen, MA; Chitsuda Wacharasindhu, MD; Sabine Mann; Raghu Kalluri, PhD; Martin C. Gregory, MD; Clifford E. Kashtan, MD; Saumil N. Merchant, MD Objective: To determine the distribution of ␣1, ␣3, and brane, in the basement membrane of cochlear blood ves- ␣5 chains of type IV collagen in the cochlea in Alport sels and Schwann cells, and within the spiral limbus. In syndrome. the control ear, we also observed strong staining for ␣3 and ␣5 chains in the basement membrane overlying the Design: Case-control study. basilar membrane and within the spiral ligament. In both cases with Alport syndrome, no immunostaining was ob- Patients: Two patients with sensorineural hearing loss served for ␣3or␣5 chains within the cochlea, whereas due to Alport syndrome. Both patients had known mu- ␣1 staining was present in locations similar to that seen tations in the COL4A5 gene. in the control ear. Main Outcome Measures: Immunostaining was used Conclusions: The results indicate that isotype switch- to study the distribution of type IV collagen (␣1, ␣3, and ing does not occur within the cochlea in Alport syn- ␣5 chains) within the cochlea. Immunostaining was also drome. The results are also consistent with the hypoth- performed in the cochlear tissues of an unaffected indi- esis that the sensorineural hearing loss in Alport syndrome vidual used as a control. may be due to alterations in cochlear micromechanics and/or dysfunction of the spiral ligament. Results: In the control ear, ␣1 staining was observed in the basement membrane overlying the basilar mem- Arch Otolaryngol Head Neck Surg. 2005;131:1007-1013 LPORT SYNDROME, AN IN- In Alport syndrome, the glomerular BM herited progressive renal within the kidney shows a characteristic disease with sensorineu- ultrastructural abnormality consisting of Author Affiliations: Ear, Nose, ral hearing loss (SNHL) diffuse thickening and splitting of the 2 and Throat Department, and ocular lesions, is lamina densa. During normal develop- University Hospital Basel, Basel, Acaused by mutations in the genes (COL4) ment, ␣1 and ␣2 chains predominate in Switzerland (Dr Zehnder); that code for the ␣3, ␣4, or ␣5 chains of the glomerular BM. As glomerular matu- Department of Otolaryngology, type IV collagen.1-3 The disease is geneti- ration progresses, the ␣3, ␣4, and ␣5 Massachusetts Eye and Ear cally heterogeneous with X-linked, auto- chains become the predominant type IV Infirmary, Boston (Drs Zehnder, somal recessive and autosomal dominant collagen chains in glomerular BM, a pro- Adams, Wacharasindhu, and forms. Most cases (approximately 85%) of cess referred to as isotype switching.2,3,5-7 In Merchant, Mr Kristiansen, and Alport syndrome are X-linked and are due Ms Mann); Department of most males with Alport syndrome, this iso- to mutations in the COL4A5 gene located type switch does not occur, as a result of Otology and Laryngology ␣ (Drs Adams and Merchant), on Xq22 that codes for the 5 chain of type which the ␣3, ␣4, and ␣5 chains are usu- Harvard Medical School, and IV collagen. More than 300 mutations of ally absent, as determined by immuno- Center for Matrix Biology, the COL4A5 gene producing X-linked Al- staining. The resulting glomerular BM in Department of Medicine, Beth port syndrome have been reported. Alport syndrome is believed to be defec- Israel Deaconess Medical Type IV collagen is the major structural tive in structure and function, causing Center (Dr Kalluri), Boston; component of basement membrane (BM) hematuria early in life and progressing to Departments of Otolaryngology ␣ and it consists of 3 chains, which make a proteinuria and renal failure. and Neuroscience (Dr Santi) triple-helical molecule.2-4 The trimer com- and Division of Pediatric ␣ ␣ ␣ ␣ In contrast to renal studies, investiga- posed of 1 and 2 chains ( 12- 21)is tions of the human inner ear in Alport syn- Nephrology, Department of present ubiquitously in BMs throughout the Pediatrics (Dr Kashtan), drome have lagged behind because of sev- body. On the other hand, trimers com- University of Minnesota, ␣ ␣ ␣ ␣ ␣ ␣ eral factors: Minneapolis; and Department posed of 3, 4, and 5( 31- 41- 51)or ␣ ␣ ␣ ␣ of Medicine, University of Utah 5 and 6( 52- 61) chains are restricted 1. It is not feasible to take a biopsy Medical Center, Salt Lake City in expression to specific BMs of the kid- sample from the cochlea during life with- (Dr Gregory). ney, inner ear, eye, and other organs. out causing severe SNHL. (REPRINTED) ARCH OTOLARYNGOL HEAD NECK SURG/ VOL 131, NOV 2005 WWW.ARCHOTO.COM 1007 ©2005 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 2. There is a paucity of human postmortem tempo- good speech discrimination. He died at age 57 years from end- ral bone material because temporal bones are not re- stage renal disease, and both temporal bones were removed 4 moved or studied as part of routine autopsies. hours after death. The left temporal bone was examined by light and electron microscopy, and findings were reported previ- 3. When temporal bones are removed and studied af- 8 ter death, tissue alterations are inevitably induced by post- ously. The right temporal bone was fixed in 10% neutral buff- ered formalin, decalcified using EDTA, trimmed so that only mortem autolysis. the inner ear remained, and was then embedded in paraffin. 4. The human temporal bone contains the delicate Serial sections were cut at a thickness of 8 µm. A representa- membranous labyrinth within an extremely dense shell tive (mid modiolar) section was stained with hematoxylin- of bone, which imposes serious technical challenges in eosin (H&E), while other sections through the cochlea were processing temporal bone tissue in a manner that al- immunostained. lows for preservation of morphology and the ability to immunostain for various proteins. CASE 2 In a recent study,8 our research team examined the Patient 2 was a man aged 31 years with X-linked Alport syn- histopathologic features of the cochlea in 9 patients with drome caused by COL4A5 mutation. This individual had a de- Alport syndrome and described abnormalities of the BM letion of exons 43-47 of the COL4A5 gene. He had bilateral SNHL of cells of the organ of Corti, as well as cellular infilling since the age of 9 years and wore amplification for several years. of the tunnel and extracellular spaces of the organ of Corti His last audiogram at age 25 years showed a downsloping 60- in 8 of the 9 cases. This particular study used a combi- to 110-dB SNHL on the right with speech discrimination of 76% nation of light and electron microscopy to study the mor- and a 60- to 90-dB SNHL on the left with speech discrimina- phologic changes in the cochlea. tion of 90%. He died at the age of 31 years from pancreatitis Knowledge of the distribution of various chains of type and complications of renal failure, and both temporal bones IV collagen in the cochlea may help in the understand- were removed 10 hours after death. The right temporal bone ing of the pathogenesis of SNHL at a cellular level. There was used in the present study. The specimen had been stored in 10% formalin for a number of years. The bone was prepared is a single extant study that examined the distribution by decalcification using EDTA and trimming so that only the of type IV collagen in the normal human inner ear. In inner ear remained, followed by embedding in paraffin and sec- 9 ␣ the study by Kleppel et al, expression of 1 chains was tioning at a thickness of 8 µm. A mid modiolar section was observed in the BM overlying the basilar membrane (ie, stained with H&E, while immunostaining was performed on the BM of cells of the organ of Corti), in the BM of coch- other sections. lear blood vessels, and in the spiral limbus and in the BM of Schwann cells. In contrast, expression of ␣3 and ␣4 CASE 3 chains was restricted to the BM overlying the basilar mem- brane. The study did not examine expression of ␣5 chains. Case 3 involved a woman aged 57 years with no otologic symp- To our knowledge, no study has described the distribu- toms (control case). This individual died as a result of a hem- tion of type IV collagen within the cochlea in Alport syn- orrhagic cerebral infarct with pulmonary thromboembolism. drome. Both temporal bones were removed 5.5 hours after death, fixed In the present study, we describe the distribution of in 10% formalin, and processed in a manner identical to that type IV collagen (␣1, ␣3, and ␣5 chains) as determined described for cases 1 and 2. Before proceeding with immunostaining on human tempo- by immunostaining within the inner ear of 2 patients with ral bones, we conducted experiments using temporal bones of SNHL due to Alport syndrome. Both patients had known CBA mice to optimize the protocol for immunostaining. The mutations in the COL4A5 gene resulting in Alport syn- temporal bones of CBA mice were fixed in 10% formalin, de- drome. Results indicate that there is selective distribu- calcified in EDTA, embedded in paraffin, and sectioned in a man- tion of ␣3 and ␣5 chains within the cochlea, including ner similar to the processing used for human tissues. Antibod- within the collagen bundles in the spiral ligament and ies against the ␣1, ␣3, and ␣5 chains of type IV collagen were limbus. Results in the cases with Alport syndrome sug- used to immunostain the animal material to optimize the gest that isotype switching for collagen does not occur protocol.
Load more

Recommended publications
  • Cochlear Partition Anatomy and Motion in Humans Differ from The
    Cochlear partition anatomy and motion in humans differ from the classic view of mammals Stefan Raufera,b,1, John J. Guinan Jra,b,c, and Hideko Heidi Nakajimaa,b,c aEaton-Peabody Laboratories, Massachusetts Eye and Ear, Boston, MA 02114; bSpeech and Hearing Bioscience and Technology Program, Harvard University, Cambridge, MA 02138; and cDepartment of Otolaryngology, Harvard Medical School, Boston, MA 02115 Edited by Christopher A. Shera, University of Southern California, Los Angeles, CA, and accepted by Editorial Board Member Thomas D. Albright June 6, 2019 (received for review January 16, 2019) Mammals detect sound through mechanosensitive cells of the assume there is no OSL motion (10–13). Additionally, the attach- cochlear organ of Corti that rest on the basilar membrane (BM). ment of the OSL to the BM and the attachment of the TM to Motions of the BM and organ of Corti have been studied at the spiral limbus (which sits above the OSL) are also consid- the cochlear base in various laboratory animals, and the assump- ered stationary. In contrast to this view, there have been reports tion has been that the cochleas of all mammals work similarly. of sound-induced OSL movement, but these reports have been In the classic view, the BM attaches to a stationary osseous spi- largely ignored in overviews of cochlear mechanics and the for- ral lamina (OSL), the tectorial membrane (TM) attaches to the mation of cochlear models (10–13). Von B´ek´esy (14), using static limbus above the stationary OSL, and the BM is the major mov- pressure, found that the CP “bent like an elastic rod that was free ing element, with a peak displacement near its center.
    [Show full text]
  • ANATOMY of EAR Basic Ear Anatomy
    ANATOMY OF EAR Basic Ear Anatomy • Expected outcomes • To understand the hearing mechanism • To be able to identify the structures of the ear Development of Ear 1. Pinna develops from 1st & 2nd Branchial arch (Hillocks of His). Starts at 6 Weeks & is complete by 20 weeks. 2. E.A.M. develops from dorsal end of 1st branchial arch starting at 6-8 weeks and is complete by 28 weeks. 3. Middle Ear development —Malleus & Incus develop between 6-8 weeks from 1st & 2nd branchial arch. Branchial arches & Development of Ear Dev. contd---- • T.M at 28 weeks from all 3 germinal layers . • Foot plate of stapes develops from otic capsule b/w 6- 8 weeks. • Inner ear develops from otic capsule starting at 5 weeks & is complete by 25 weeks. • Development of external/middle/inner ear is independent of each other. Development of ear External Ear • It consists of - Pinna and External auditory meatus. Pinna • It is made up of fibro elastic cartilage covered by skin and connected to the surrounding parts by ligaments and muscles. • Various landmarks on the pinna are helix, antihelix, lobule, tragus, concha, scaphoid fossa and triangular fossa • Pinna has two surfaces i.e. medial or cranial surface and a lateral surface . • Cymba concha lies between crus helix and crus antihelix. It is an important landmark for mastoid antrum. Anatomy of external ear • Landmarks of pinna Anatomy of external ear • Bat-Ear is the most common congenital anomaly of pinna in which antihelix has not developed and excessive conchal cartilage is present. • Corrections of Pinna defects are done at 6 years of age.
    [Show full text]
  • The Membranous Labyrinth in Vivo from High-Resolution Temporal CT Data
    bioRxiv preprint doi: https://doi.org/10.1101/318030; this version posted May 9, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. The Membranous Labyrinth in vivo from high-resolution Temporal CT data Hisaya Tanioka¹* ¹Department of Radiology, Tanioka Clinic *Corresponding author Hisaya Tanioka, MD, PhD Tanioka Clinic Tanioka Bldg. 3F, 6-24-2 Honkomagome Bunkyo-ku, Tokyo 113-0021 Japan Tel & Fax: 81-3-3945-5199 E-mail: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/318030; this version posted May 9, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. The Membranous Labyrinth in vivo from high-resolution Temporal CT data bioRxiv preprint doi: https://doi.org/10.1101/318030; this version posted May 9, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. ABSTRACT A prerequisite for the modeling and understanding of the inner ear mechanics needs the accurate created membranous labyrinth. I present a semi-automated methodology for accurate reconstruction of the membranous labyrinth in vivo from high-resolution temporal bone CT data of normal human subjects.
    [Show full text]
  • Characteristic Anatomical Structures of Rat Temporal Bone
    HOSTED BY Available online at www.sciencedirect.com ScienceDirect Journal of Otology 10 (2015) 118e124 www.journals.elsevier.com/journal-of-otology/ Characteristic anatomical structures of rat temporal bone Peng Li a,b, Kelei Gao b,c, Dalian Ding a,b,c,*, Richard Salvi b,c a Department of Otolaryngology, Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China b Center for Hearing and Deafness, State University of New York at Buffalo, Buffalo, NY 14214, USA c Department of Otolaryngology, Head and Neck Surgery, Xiangya Hospital, Central South University, Hunan 410013, China Abstract As most gene sequences and functional structures of internal organs in rats have been well studied, rat models are widely used in experi- mental medical studies. A large number of descriptions and atlas of the rat temporal bone have been published, but some detailed anatomy of its surface and inside structures remains to be studied. By focusing on some unique characteristics of the rat temporal bone, the current paper aims to provide more accurate and detailed information on rat temporal bone anatomy in an attempt to complete missing or unclear areas in the existed knowledge. We also hope this paper can lay a solid foundation for experimental rat temporal bone surgeries, and promote information exchange among colleagues, as well as providing useful guidance for novice researchers in the field of hearing research involving rats. Copyright © 2015 The Authors. Production & hosting by Elsevier (Singapore) Pte Ltd On behalf of PLA General Hospital Department of Otolaryngology Head and Neck Surgery. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/ by-nc-nd/4.0/).
    [Show full text]
  • Anatomic Moment
    Anatomic Moment Hearing, I: The Cochlea David L. Daniels, Joel D. Swartz, H. Ric Harnsberger, John L. Ulmer, Katherine A. Shaffer, and Leighton Mark The purpose of the ear is to transform me- cochlear recess, which lies on the medial wall of chanical energy (sound) into electric energy. the vestibule (Fig 3). As these sound waves The external ear collects and directs the sound. enter the perilymph of the scala vestibuli, they The middle ear converts the sound to fluid mo- are transmitted through the vestibular mem- tion. The inner ear, specifically the cochlea, brane into the endolymph of the cochlear duct, transforms fluid motion into electric energy. causing displacement of the basilar membrane, The cochlea is a coiled structure consisting of which stimulates the hair cell receptors of the two and three quarter turns (Figs 1 and 2). If it organ of Corti (Figs 4–7) (4, 5). It is the move- were elongated, the cochlea would be approxi- ment of hair cells that generates the electric mately 30 mm in length. The fluid-filled spaces potentials that are converted into action poten- of the cochlea are comprised of three parallel tials in the auditory nerve fibers. The basilar canals: an outer scala vestibuli (ascending spi- membrane varies in width and tension from ral), an inner scala tympani (descending spi- base to apex. As a result, different portions of ral), and the central cochlear duct (scala media) the membrane respond to different auditory fre- (1–7). The scala vestibuli and scala tympani quencies (2, 5). These perilymphatic waves are contain perilymph, a substance similar in com- transmitted via the apex of the cochlea (helico- position to cerebrospinal fluid.
    [Show full text]
  • Mmubn000001 20756843X.Pdf
    PDF hosted at the Radboud Repository of the Radboud University Nijmegen The following full text is a publisher's version. For additional information about this publication click this link. http://hdl.handle.net/2066/147581 Please be advised that this information was generated on 2021-10-07 and may be subject to change. CATION TRANSPORT AND COCHLEAR FUNCTION CATION TRANSPORT AND COCHLEAR FUNCTION PROMOTORES: Prof. Dr. S. L. BONTING EN Prof. Dr. W. F. B. BRINKMAN CATION TRANSPORT AND COCHLEAR FUNCTION PROEFSCHRIFT TER VERKRIJGING VAN DE GRAAD VAN DOCTOR IN DE WISKUNDE EN NATUURWETENSCHAPPEN AAN DE KATHOLIEKE UNIVERSITEIT TE NIJMEGEN, OP GEZAG VAN DE RECTOR MAGNIFICUS DR. G. BRENNINKMEIJER, HOOGLERAAR IN DE FACULTEIT DER SOCIALE WETENSCHAPPEN, VOLGENS BESLUIT VAN DE SENAAT IN HET OPENBAAR TE VERDEDIGEN OP VRIJDAG 19 DECEMBER 1969 DES NAMIDDAGS TE 2 UUR DOOR WILLIBRORDUS KUIJPERS GEBOREN TE KLOOSTERZANDE 1969 CENTRALE DRUKKERIJ NIJMEGEN I am greatly indebted to Dr. J. F. G. Siegers for his interest and many valuable discussions throughout the course of this investigation. The technical assistance of Miss A. C. H. Janssen, Mr. A. C. van der Vleuten and Mr. P. Spaan and co-workers was greatly appreciated. I also wish to express my gratitude to Miss. A. E. Gonsalvcs and Miss. G. Kuijpers for typing and to Mrs. M. Duncan for correcting the ma­ nuscript. The diagrams were prepared by Mr W. Maas and Mr. C. Reckers and the micro- photographs by Mr. A. Reijnen of the department of medical illustration. Aan mijn Ouders, l Thea, Annemarie, Katrien en Michiel. CONTENTS GENERAL INTRODUCTION ...
    [Show full text]
  • A Place Principle for Vertigo
    Auris Nasus Larynx 35 (2008) 1–10 www.elsevier.com/locate/anl A place principle for vertigo Richard R. Gacek * Department of Otolaryngology, Head and Neck Surgery, University of Massachusetts Medical School, Worcester, MA 01655, USA Received 16 March 2007; accepted 13 April 2007 Available online 24 October 2007 Abstract Objective: To provide a road map of the vestibular labyrinth and its innervation leading to a place principle for different forms of vertigo. Method: The literature describing the anatomy and physiology of the vestibular system was reviewed. Results: Different forms of vertigo may be determined by the type of sense organ, type of ganglion cell and location in the vestibular nerve. Conclusion: Partial lesions (viral) of the vestibular ganglion are manifested as various forms of vertigo. # 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Vertigo; Vestibular nerve; Pathology Contents 1. Introduction . ............................................................................... 1 2. Sense organ. ............................................................................... 2 3. Ganglion cells ............................................................................... 4 4. Hair cells . ............................................................................... 5 5. Hair cell polarization . ....................................................................... 5 6. Efferent vestibular system ....................................................................... 8 7. A place principle for vertigo . .................................................................
    [Show full text]
  • Inner Ear Defects and Hearing Loss in Mice Lacking the Collagen Receptor
    Laboratory Investigation (2008) 88, 27–37 & 2008 USCAP, Inc All rights reserved 0023-6837/08 $30.00 Inner ear defects and hearing loss in mice lacking the collagen receptor DDR1 Angela M Meyer zum Gottesberge1, Oliver Gross2, Ursula Becker-Lendzian1, Thomas Massing1 and Wolfgang F Vogel3 Discoidin domain receptor 1 (DDR1) is a tyrosine kinase receptor that is activated by native collagen. The physiological functions of DDR1 include matrix homeostasis and cell growth, adhesion, branching, and migration, but the specific role of DDR1 in the development and function of the inner ear has not been analyzed. Here, we show that deletion of the DDR1 gene in mouse is associated with a severe decrease in auditory function and substantial structural alterations in the inner ear. Immunohistochemical analysis demonstrated DDR1 expression in several locations in the cochlea, mostly associated with basement membrane and fibrillar collagens; in particular in basal cells of the stria vascularis, type III fibrocytes, and cells lining the basilar membrane of the organ of Corti. In the stria vascularis, loss of DDR1 function resulted in altered morphology of the basal cells and accumulation of electron-dense matrix within the strial epithelial layer in conjunction with a focal and progressive deterioration of strial cells. Cell types in proximity to the basilar membrane, such as Claudius’, inner and outer sulcus cells, also showed marked ultrastructural alterations. Changes in the organ of Corti, such as deterioration of the supporting cells, specifically the outer hair cells, Deiters’, Hensen’s and bordering cells, are likely to interfere with mechanical properties of the organ and may be responsible for the hearing loss observed in DDR1-null mice.
    [Show full text]
  • Microstructures of the Osseous Spiral Laminae in the Bat Cochlea: a Scanning Electron Microscopic Study
    Arch. Histol. Cytol., Vol. 55, No. 3 (1992) p. 315-319 Microstructures of the Osseous Spiral Laminae in the Bat Cochlea: A Scanning Electron Microscopic Study Babi r KUcUK2 and Kazuhiro ABE1 Department of Anatomy, Hokkaido University School of Medicine, Sapporo, Hokkaido; and Department of Otolaryngology2, Tokai University School of Medicine, Isehara, Kanagawa, Japan Received May 22, 1992 Summary. The architecture and surface structures of dary osseous spiral laminae. High frequency sounds the primary and secondary osseous spiral laminae in the vibrate the membrane in the basal regions of the cochlea of the bat, an animal able to hear high fre- cochlear duct, while relatively lower frequency quency sounds, were examined by scanning electron sounds vibrate the membrane in the apical regions microscopy to understand the micromechanical adapta- (BEKESY, 1960) . Using the mouse cochlea, we have tions of the bony supportive elements in the inner ear to suggested that the regional vibration pattern of the the specific hearing function. The bat used was Myotis frater kaguyae. basilar membrane is closely related to the base-to- The myotis bat cochlea was seen to consist of a hook apex variations in the morphology of the osseous and a spiral portion with one and three-quarter turns spiral laminae (KUcUK and ABE, 1989). It is known and was characterized by: 1) a distinct ridge-like pro- that the bat cochlea is sensitive to sounds in the very jection running spirally along the middle line on the high frequency range. In fact, the frequencies of the vestibular leaf of the primary osseous spiral lamina; 2) sounds that stimulate the basilar membrane in the a wide secondary osseous spiral lamina; and 3) a narrow bat cochlea are higher than those that stimulate the spiral fissure between the primary and secondary osse- basal regions of the basilar membrane in the mouse ous spiral laminae.
    [Show full text]
  • Otoancorin, an Inner Ear Protein Restricted To
    Otoancorin, an inner ear protein restricted to the interface between the apical surface of sensory epithelia and their overlying acellular gels, is defective in autosomal recessive deafness DFNB22 Ingrid Zwaenepoel*, Mirna Mustapha*, Michel Leibovici*, Elisabeth Verpy*, Richard Goodyear†, Xue Zhong Liu‡, Sylvie Nouaille*, Walter E. Nance§, Moien Kanaan¶, Karen B. Avrahamʈ, Fredj Tekaia**, Jacques Loiselet††, Marc Lathrop‡‡, Guy Richardson†, and Christine Petit*¶¶ *Unite´deGe´ne´ tique des De´ficits Sensoriels, Centre National de la Recherche Scientifique, Unite´de Recherche Associe´e 1968, and **Unite´deGe´ne´ tique Mole´culaire des Levures, Centre National de la Recherche Scientifique, Unite´de Recherche Associe´e 2171, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France; †School of Biological Sciences, The University of Sussex, Falmer, Brighton, BN1 9QG, United Kingdom; ‡Department of Otolaryngology, University of Miami, Miami, FL 33101; §Department of Human Genetics, Virginia Commonwealth University, 1101 East Marshall Street, Richmond, VA 23219; ¶Molecular Genetics, Life Science Department, Bethlehem University POB 9, Palestinian Authority; ʈDepartment of Human Genetics and Molecular Medicine, Tel Aviv University, Tel Aviv 69978, Israel; ††Laboratoire de Biologie Mole´culaire, Faculte´deMe´ decine, Universite´Saint-Joseph, Beyrouth, Lebanon; and ‡‡Centre National de Ge´notypage, 91057 Evry, France Edited by Thaddeus P. Dryja, Harvard Medical School, Boston, MA, and approved February 21, 2002 (received for review October 1, 2001) A 3,673-bp murine cDNA predicted to encode a glycosylphosphati- collagenase-insensitive striated-sheet matrix (6). Otogelin is asso- dylinositol-anchored protein of 1,088 amino acids was isolated ciated mainly with the collagen fibril bundles (3, 7), whereas ␣- and during a study aimed at identifying transcripts specifically ex- ␤-tectorin are major components of the striated-sheet matrix (8, 9).
    [Show full text]
  • Degeneration and Reorganization of Vestibular Epithelia After Local Aminoglycoside Application in the Mammalian Inner Ear
    Scanning Microscopy Volume 7 Number 2 Article 16 3-5-1993 Degeneration and Reorganization of Vestibular Epithelia after Local Aminoglycoside Application in the Mammalian Inner Ear J. Dupont University of Michigan, Ann Arbor A. Guilhaume Université de Bordeaux II J. -M. Aran Université de Bordeaux II Follow this and additional works at: https://digitalcommons.usu.edu/microscopy Part of the Biology Commons Recommended Citation Dupont, J.; Guilhaume, A.; and Aran, J. -M. (1993) "Degeneration and Reorganization of Vestibular Epithelia after Local Aminoglycoside Application in the Mammalian Inner Ear," Scanning Microscopy: Vol. 7 : No. 2 , Article 16. Available at: https://digitalcommons.usu.edu/microscopy/vol7/iss2/16 This Article is brought to you for free and open access by the Western Dairy Center at DigitalCommons@USU. It has been accepted for inclusion in Scanning Microscopy by an authorized administrator of DigitalCommons@USU. For more information, please contact [email protected]. Scanning Microscopy, Vol. 7, No. 2, 1993 (Pages 597-612) 0891-7035/93$5.00+ .00 Scanning Microscopy International, Chicago (AMF O'Hare), IL 60666 USA DEGENERATION AND REORGANIZATION OF VESTIBULAR EPITHELIA AFTER LOCAL AMINOGLYCOSIDE APPLICATION IN THE MAMMALIAN INNER EAR J. Dupont*· 1, A. Guilhaume and J.-M. Aran Laboratoire d' Audiologie Experimentale, INS ERM U .229 and Universite de Bordeaux II, H6pital Pellegrin, place Amelie Raba Leon, 33076 BORDEAUX, FRANCE 1Present Address: Kresge Hearing Research Institute, University of Michigan, Ann Arbor, MI,
    [Show full text]
  • In Vitro Gentamicin Exposure Alters Caveolae Protein Profile in Cochlear Spiral Ligament Pericytes Elisa Ghelfi1* , Yohann Grondin1, Emil J
    Ghelfi et al. Proteome Science (2018) 16:7 https://doi.org/10.1186/s12953-018-0132-x RESEARCH Open Access In vitro gentamicin exposure alters caveolae protein profile in cochlear spiral ligament pericytes Elisa Ghelfi1* , Yohann Grondin1, Emil J. Millet1, Adam Bartos1, Magda Bortoni1, Clara Oliveira Gomes dos Santos1,2, Humberto J. Trevino-Villarreal3, Rosalinda Sepulveda1,4 and Rick Rogers1 Abstract Background: The aminoglycoside antibiotic gentamicin is an ototoxic drug and has been used experimentally to investigate cochlear damage induced by noise. We have investigated the changes in the protein profile associated with caveolae in gentamicin treated and untreated spiral ligament (SL) pericytes, specialized cells in the blood labyrinth barrier of the inner ear microvasculature. Pericytes from various microvascular beds express caveolae, protein and cholesterol rich microdomains, which can undergo endocytosis and transcytosis to transport small molecules in and out the cells. A different protein profile in transport-specialized caveolae may induce pathological changes affecting the integrity of the blood labyrinth barrier and ultimately contributing to hearing loss. Method: Caveolae isolation from treated and untreated cells is achieved through ultracentrifugation of the lysates in discontinuous gradients. Mass spectrometry (LC-MS/MS) analysis identifies the proteins in the two groups. Proteins segregating with caveolae isolated from untreated SL pericytes are then compared to caveolae isolated from SL pericytes treated with the gentamicin for 24 h. Data are analyzed using bioinformatic tools. Results: The caveolae proteome in gentamicin treated cells shows that 40% of total proteins are uniquely associated with caveolae during the treatment, and 15% of the proteins normally associated with caveolae in untreated cell are suppressed.
    [Show full text]