Human Molecular Genetics, 2001, Vol. 10, No. 2 153-161
© 2001 Oxford University Press
Targeted disruption of mouse Pds provides insight about the inner-ear defects encountered in Pendred syndrome
1Genome Technology Branch, 5Embryonic Stem Cell/Transgenic Mouse Core and 6Office of Laboratory Animal Medicine, National Human Genome Research Institute and 2Laboratory of Cellular Biology, 3Laboratory of Molecular Genetics and 4Laboratory of Molecular Biology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA
Following the positional cloning of PDS, the gene mutated in the deafness/goitre disorder Pendred syndrome (PS), numerous studies have focused on defining the role of PDS in deafness and PS as well as elucidating the function of the PDS-encoded protein (pendrin). To facilitate these efforts and to provide a system for more detailed study of the inner-ear defects that occur in the absence of pendrin, we have generated a Pds-knockout mouse. Pds–/– mice are completely deaf and also display signs of vestibular dysfunction. The inner ears of these mice appear to develop normally until embryonic day 15, after which time severe endolymphatic dilatation occurs, reminiscent of that seen radiologically in deaf individuals with PDS mutations. Additionally, in the second postnatal week, severe degeneration of sensory cells and malformation of otoconia and otoconial membranes occur, as revealed by scanning electron and fluorescence confocal microscopy. The ultrastructural defects seen in the Pds–/– mice provide important clues about the mechanisms responsible for the inner-ear pathology associated with PDS mutations.
+ To whom correspondence should be addressed. Tel: +1 301 402 0201; Fax: +1 301 402 4735; Email: egreen@nhgri.nih.gov
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Bizhanova and P. Kopp The Sodium-Iodide Symporter NIS and Pendrin in Iodide Homeostasis of the Thyroid Endocrinology, March 1, 2009; 150(3): 1084 - 1090. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Frank, N. Groger, M. Diener, C. Becker, T. Braun, and T. Boettger Lactaturia and Loss of Sodium-dependent Lactate Uptake in the Colon of SLC5A8-deficient Mice J. Biol. Chem., September 5, 2008; 283(36): 24729 - 24737. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Nakagami, S. Favoreto Jr, G. Zhen, S.-W. Park, L. T. Nguyenvu, D. A. Kuperman, G. M. Dolganov, X. Huang, H. A. Boushey, P. C. Avila, et al. The Epithelial Anion Transporter Pendrin Is Induced by Allergy and Rhinovirus Infection, Regulates Airway Surface Liquid, and Increases Airway Reactivity and Inflammation in an Asthma Model J. Immunol., August 1, 2008; 181(3): 2203 - 2210. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Nakao, S. Kanaji, S. Ohta, H. Matsushita, K. Arima, N. Yuyama, M. Yamaya, K. Nakayama, H. Kubo, M. Watanabe, et al. Identification of Pendrin as a Common Mediator for Mucus Production in Bronchial Asthma and Chronic Obstructive Pulmonary Disease J. Immunol., May 1, 2008; 180(9): 6262 - 6269. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Palos, M. E. R. Garcia-Rendueles, D. Araujo-Vilar, M. J. Obregon, R. M. Calvo, J. Cameselle-Teijeiro, S. B. Bravo, O. Perez-Guerra, L. Loidi, B. Czarnocka, et al. Pendred Syndrome in Two Galician Families: Insights into Clinical Phenotypes through Cellular, Genetic, and Molecular Studies J. Clin. Endocrinol. Metab., January 1, 2008; 93(1): 267 - 277. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Singh and P. Wangemann Free radical stress-mediated loss of Kcnj10 protein expression in stria vascularis contributes to deafness in Pendred syndrome mouse model Am J Physiol Renal Physiol, January 1, 2008; 294(1): F139 - F148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. P. Hatch, C. A. Noyes, X. Wang, T. J. Wright, and S. L. Mansour Fgf3 is required for dorsal patterning and morphogenesis of the inner ear epithelium Development, October 15, 2007; 134(20): 3615 - 3625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. H. Kim, V. Pech, K. B. Spencer, W. H. Beierwaltes, L. A. Everett, E. D. Green, W. Shin, J. W. Verlander, R. L. Sutliff, and S. M. Wall Reduced ENaC protein abundance contributes to the lower blood pressure observed in pendrin-null mice Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1314 - F1324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Toure, P. Lhuillier, J. A. Gossen, C. W. Kuil, D. Lhote, B. Jegou, D. Escalier, and G. Gacon The Testis Anion Transporter 1 (Slc26a8) is required for sperm terminal differentiation and male fertility in the mouse Hum. Mol. Genet., August 1, 2007; 16(15): 1783 - 1793. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. R. Johnson, C. C. Marden, P. Ward-Bailey, L. H. Gagnon, R. T. Bronson, and L. R. Donahue Congenital Hypothyroidism, Dwarfism, and Hearing Impairment Caused by a Missense Mutation in the Mouse Dual Oxidase 2 Gene, Duox2 Mol. Endocrinol., July 1, 2007; 21(7): 1593 - 1602. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Gao, S. F. Maison, X. Wu, K. Hirose, S. M. Jones, I. Bayazitov, Y. Tian, G. Mittleman, D. B. Matthews, S. S. Zakharenko, et al. Orphan Glutamate Receptor {delta}1 Subunit Required for High-Frequency Hearing Mol. Cell. Biol., June 15, 2007; 27(12): 4500 - 4512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Nakaya, D. G. Harbidge, P. Wangemann, B. D. Schultz, E. D. Green, S. M. Wall, and D. C. Marcus Lack of pendrin HCO3- transport elevates vestibular endolymphatic [Ca2+] by inhibition of acid-sensitive TRPV5 and TRPV6 channels Am J Physiol Renal Physiol, May 1, 2007; 292(5): F1314 - F1321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Wangemann, K. Nakaya, T. Wu, R. J. Maganti, E. M. Itza, J. D. Sanneman, D. G. Harbidge, S. Billings, and D. C. Marcus Loss of cochlear HCO3- secretion causes deafness via endolymphatic acidification and inhibition of Ca2+ reabsorption in a Pendred syndrome mouse model Am J Physiol Renal Physiol, May 1, 2007; 292(5): F1345 - F1353. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kono, I. A. Belyantseva, A. Skoura, G. I. Frolenkov, M. F. Starost, J. L. Dreier, D. Lidington, S.-S. Bolz, T. B. Friedman, T. Hla, et al. Deafness and Stria Vascularis Defects in S1P2 Receptor-null Mice J. Biol. Chem., April 6, 2007; 282(14): 10690 - 10696. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Pech, Y. H. Kim, A. M. Weinstein, L. A. Everett, T. D. Pham, and S. M. Wall Angiotensin II increases chloride absorption in the cortical collecting duct in mice through a pendrin-dependent mechanism Am J Physiol Renal Physiol, March 1, 2007; 292(3): F914 - F920. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Madden, M. Halsted, J. Meinzen-Derr, D. Bardo, M. Boston, E. Arjmand, C. Nishimura, T. Yang, C. Benton, V. Das, et al. The Influence of Mutations in the SLC26A4 Gene on the Temporal Bone in a Population With Enlarged Vestibular Aqueduct Arch Otolaryngol Head Neck Surg, February 1, 2007; 133(2): 162 - 168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. H. Gagnon, C. M. Longo-Guess, M. Berryman, J.-B. Shin, K. W. Saylor, H. Yu, P. G. Gillespie, and K. R. Johnson The Chloride Intracellular Channel Protein CLIC5 Is Expressed at High Levels in Hair Cell Stereocilia and Is Essential for Normal Inner Ear Function J. Neurosci., October 4, 2006; 26(40): 10188 - 10198. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Wangemann Supporting sensory transduction: cochlear fluid homeostasis and the endocochlear potential J. Physiol., October 1, 2006; 576(1): 11 - 21. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Verlander, Y. H. Kim, W. Shin, T. D. Pham, K. A. Hassell, W. H. Beierwaltes, E. D. Green, L. Everett, S. W. Matthews, and S. M. Wall Dietary Cl- restriction upregulates pendrin expression within the apical plasma membrane of type B intercalated cells Am J Physiol Renal Physiol, October 1, 2006; 291(4): F833 - F839. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-F. van den Hove, K. Croizet-Berger, F. Jouret, S. E. Guggino, W. B. Guggino, O. Devuyst, and P. J. Courtoy The Loss of the Chloride Channel, ClC-5, Delays Apical Iodide Efflux and Induces a Euthyroid Goiter in the Mouse Thyroid Gland Endocrinology, March 1, 2006; 147(3): 1287 - 1296. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-H. Kim, J. W. Verlander, S. W. Matthews, I. Kurtz, W. Shin, I. D. Weiner, L. A. Everett, E. D. Green, S. Nielsen, and S. M. Wall Intercalated cell H+/OH- transporter expression is reduced in Slc26a4 null mice Am J Physiol Renal Physiol, December 1, 2005; 289(6): F1262 - F1272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Lin, R. Cantos, M. Patente, and D. K. Wu Gbx2 is required for the morphogenesis of the mouse inner ear: a downstream candidate of hindbrain signaling Development, May 15, 2005; 132(10): 2309 - 2318. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Goldfeld, B. Glaser, E. Nassir, J. M. Gomori, E. Hazani, and N. Bishara CT of the Ear in Pendred Syndrome Radiology, May 1, 2005; 235(2): 537 - 540. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Wall, Y. H. Kim, L. Stanley, D. M. Glapion, L. A. Everett, E. D. Green, and J. W. Verlander NaCl Restriction Upregulates Renal Slc26a4 Through Subcellular Redistribution: Role in Cl- Conservation Hypertension, December 1, 2004; 44(6): 982 - 987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Napiontek, G. Borck, W. Muller-Forell, N. Pfarr, A. Bohnert, A. Keilmann, and J. Pohlenz Intrafamilial Variability of the Deafness and Goiter Phenotype in Pendred Syndrome Caused by a T416P Mutation in the SLC26A4 Gene J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5347 - 5351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Dou, J. Xu, Z. Wang, A. N. Smith, M. Soleimani, F. E. Karet, J. H. Greinwald Jr, and D. Choo Co-expression of Pendrin, Vacuolar H+-ATPase {alpha}4-Subunit and Carbonic Anhydrase II in Epithelial Cells of the Murine Endolymphatic Sac J. Histochem. Cytochem., October 1, 2004; 52(10): 1377 - 1384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Gillam, A. R. Sidhaye, E. J. Lee, J. Rutishauser, C. W. Stephan, and P. Kopp Functional Characterization of Pendrin in a Polarized Cell System: EVIDENCE FOR PENDRIN-MEDIATED APICAL IODIDE EFFLUX J. Biol. Chem., March 26, 2004; 279(13): 13004 - 13010. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Sollner, M. Burghammer, E. Busch-Nentwich, J. Berger, H. Schwarz, C. Riekel, and T. Nicolson Control of Crystal Size and Lattice Formation by Starmaker in Otolith Biomineralization Science, October 10, 2003; 302(5643): 282 - 286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Verlander, K. A. Hassell, I. E. Royaux, D. M. Glapion, M.-E. Wang, L. A. Everett, E. D. Green, and S. M. Wall Deoxycorticosterone Upregulates PDS (Slc26a4) in Mouse Kidney: Role of Pendrin in Mineralocorticoid-Induced Hypertension Hypertension, September 1, 2003; 42(3): 356 - 362. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kudo, S. Kure, K. Ikeda, A.-P. Xia, Y. Katori, M. Suzuki, K. Kojima, A. Ichinohe, Y. Suzuki, Y. Aoki, et al. Transgenic expression of a dominant-negative connexin26 causes degeneration of the organ of Corti and non-syndromic deafness Hum. Mol. Genet., May 1, 2003; 12(9): 995 - 1004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hulander, A. E. Kiernan, S. R. Blomqvist, P. Carlsson, E.-J. Samuelsson, B. R. Johansson, K. P. Steel, and S. Enerback Lack of pendrin expression leads to deafness and expansion of the endolymphatic compartment in inner ears of Foxi1 null mutant mice Development, May 1, 2003; 130(9): 2013 - 2025. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Hurle, E. Ignatova, S. M. Massironi, T. Mashimo, X. Rios, I. Thalmann, R. Thalmann, and D. M. Ornitz Non-syndromic vestibular disorder with otoconial agenesis in tilted/mergulhador mice caused by mutations in otopetrin 1 Hum. Mol. Genet., April 1, 2003; 12(7): 777 - 789. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H-J Park, S Shaukat, X-Z Liu, S H Hahn, S Naz, M Ghosh, H-N Kim, S-K Moon, S Abe, K Tukamoto, et al. Origins and frequencies of SLC26A4 (PDS) mutations in east and south Asians: global implications for the epidemiology of deafness J. Med. Genet., April 1, 2003; 40(4): 242 - 248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. P. Karniski, T. Wang, L. A. Everett, E. D. Green, G. Giebisch, and P. S. Aronson Formate-stimulated NaCl absorption in the proximal tubule is independent of the pendrin protein Am J Physiol Renal Physiol, November 1, 2002; 283(5): F952 - F956. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Rotman-Pikielny, K. Hirschberg, P. Maruvada, K. Suzuki, I. E. Royaux, E. D. Green, L. D. Kohn, J. Lippincott-Schwartz, and P. M. Yen Retention of pendrin in the endoplasmic reticulum is a major mechanism for Pendred syndrome Hum. Mol. Genet., October 2, 2002; 11(21): 2625 - 2633. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Strott Sulfonation and Molecular Action Endocr. Rev., October 1, 2002; 23(5): 703 - 732. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Bitner-Glindzicz Hereditary deafness and phenotyping in humans Br. Med. Bull., October 1, 2002; 63(1): 73 - 94. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Kopp Perspective: Genetic Defects in the Etiology of Congenital Hypothyroidism Endocrinology, June 1, 2002; 143(6): 2019 - 2024. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. Morton Genetics, genomics and gene discovery in the auditory system Hum. Mol. Genet., May 15, 2002; 11(10): 1229 - 1240. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Taylor, R. A. Metcalfe, P. F. Watson, A. P. Weetman, and R. C. Trembath Mutations of the PDS Gene, Encoding Pendrin, Are Associated with Protein Mislocalization and Loss of Iodide Efflux: Implications for Thyroid Dysfunction in Pendred Syndrome J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1778 - 1784. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. E. Royaux, S. M. Wall, L. P. Karniski, L. A. Everett, K. Suzuki, M. A. Knepper, and E. D. Green Pendrin, encoded by the Pendred syndrome gene, resides in the apical region of renal intercalated cells and mediates bicarbonate secretion PNAS, March 27, 2001; 98(7): 4221 - 4226. [Abstract] [Full Text] [PDF]
|
|