HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: fj.07-104836v1 22/9/3216    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lu, D. C. Articles by Verkman, A. S. Search for Related Content PubMed PubMed Citation Articles by Lu, D. C. Articles by Verkman, A. S.

Impaired olfaction in mice lacking aquaporin-4 water channels

Daniel C. Lu^*,,, Hua Zhang^*,, Zsolt Zador^*,, and A. S. Verkman^*,,1

^* Department of Medicine,

Department of Physiology, and

Department of Neurological Surgery, University of California, San Francisco, California, USA

¹Correspondence: 1246 Health Sciences East Tower, University of California, San Francisco, CA 94143-0521, USA. E-mail: alan.verkman{at}ucsf.edu

Aquaporin-4 (AQP4) is a water-selective transport protein expressed in glial cells throughout the central nervous system. AQP4 deletion in mice produces alterations in several neuroexcitation phenomena, including hearing, vision, epilepsy, and cortical spreading depression. Here, we report defective olfaction and electroolfactogram responses in AQP4-null mice. Immunofluorescence indicated strong AQP4 expression in supportive cells of the nasal olfactory epithelium. The olfactory epithelium in AQP4-null mice had identical appearance, but did not express AQP4, and had 12-fold reduced osmotic water permeability. Behavioral analysis showed greatly impaired olfaction in AQP4-null mice, with latency times of 17 ± 0.7 vs. 55 ± 5 s in wild-type vs. AQP4-null mice in a buried food pellet test, which was confirmed using an olfactory maze test. Electroolfactogram voltage responses to multiple odorants were reduced in AQP4-null mice, with maximal responses to triethylamine of 0.80 ± 0.07 vs. 0.28 ± 0.03 mV. Similar olfaction and electroolfactogram defects were found in outbred (CD1) and inbred (C57/bl6) mouse genetic backgrounds. Our results establish AQP4 as a novel determinant of olfaction, the deficiency of which probably impairs extracellular space K⁺ buffering in the olfactory epithelium.—Lu, D. C., Zhang, H., Zador, Z., Verkman, A. S. Impaired olfaction in mice lacking aquaporin-4 water channels.

Key Words: smell • water permeability • olfactogram

This article has been cited by other articles:

				A. S. Verkman Aquaporins: translating bench research to human disease J. Exp. Biol., June 1, 2009; 212(11): 1707 - 1715. [Abstract] [Full Text] [PDF]