Mice lacking inositol 1,4,5-trisphosphate receptors exhibit dry eye
Tear secretion is important as it supplies water to the ocular surface and keeps eyes moist. Both the parasympathetic and sympathetic pathways contribute to tear secretion. Although intracellular Ca2+ elevation in the acinar cells of lacrimal glands is a crucial event for tear secretion in both the...
Gespeichert in:
| Veröffentlicht in: | PloS one 2014-06, Vol.9 (6), p.e99205-e99205 |
|---|---|
| Hauptverfasser: | , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e99205 |
|---|---|
| container_issue | 6 |
| container_start_page | e99205 |
| container_title | PloS one |
| container_volume | 9 |
| creator | Inaba, Takaaki Hisatsune, Chihiro Sasaki, Yasumasa Ogawa, Yoko Ebisui, Etsuko Ogawa, Naoko Matsui, Minoru Takeuchi, Tsutomu Mikoshiba, Katsuhiko Tsubota, Kazuo |
| description | Tear secretion is important as it supplies water to the ocular surface and keeps eyes moist. Both the parasympathetic and sympathetic pathways contribute to tear secretion. Although intracellular Ca2+ elevation in the acinar cells of lacrimal glands is a crucial event for tear secretion in both the pathways, the Ca2+ channel, which is responsible for the Ca2+ elevation in the sympathetic pathway, has not been sufficiently analyzed. In this study, we examined tear secretion in mice lacking the inositol 1,4,5-trisphosphate receptor (IP3R) types 2 and 3 (Itpr2-/-;Itpr3-/-double-knockout mice). We found that tear secretion in both the parasympathetic and sympathetic pathways was abolished in Itpr2-/-;Itpr3-/- mice. Intracellular Ca2+ elevation in lacrimal acinar cells after acetylcholine and epinephrine stimulation was abolished in Itpr2-/-;Itpr3-/- mice. Consequently, Itpr2-/-;Itpr3-/- mice exhibited keratoconjunctival alteration and corneal epithelial barrier disruption. Inflammatory cell infiltration into the lacrimal glands and elevation of serum autoantibodies, a representative marker for Sjögren's syndrome (SS) in humans, were also detected in older Itpr2-/-;Itpr3-/- mice. These results suggested that IP3Rs are essential for tear secretion in both parasympathetic and sympathetic pathways and that Itpr2-/-;Itpr3-/- mice could be a new dry eye mouse model with symptoms that mimic those of SS. |
| doi_str_mv | 10.1371/journal.pone.0099205 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1532987220</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A418707798</galeid><doaj_id>oai_doaj_org_article_55f3bca5939b411b85acbf975d3b1450</doaj_id><sourcerecordid>A418707798</sourcerecordid><originalsourceid>FETCH-LOGICAL-c758t-fb53dd67e649b702d1cb2901b23ca9c56add2fa7b6af7cdbae51453a1b90eaa43</originalsourceid><addsrcrecordid>eNqNkl1r2zAUhs3YWNts_2BshsHYoMkkS7Ksm0EJ-wh0FPZ1K45kOVHmWJkkl-bfT2ncEo9eDCEkpOe85xzpzbIXGM0w4fj92vW-g3a2dZ2ZISREgdij7BQLUkzLApHHR_uT7CyENUKMVGX5NDspqEC4ovQ0m3-12uQt6N-2W-a2c8FG1-b4nJ6zafQ2bFcuTYgm90abbXQ-5OZmZZWNee13udmZZ9mTBtpgng_rJPv56eOP-Zfp5dXnxfzicqo5q-K0UYzUdclNSYXiqKixVkWqQxVEg9CshLouGuCqhIbrWoFhmDICWAlkACiZZK8OutvWBTn0HyRmpBAVL1Kfk2xxIGoHa7n1dgN-Jx1YeXvg_FKCj1a3RjLWEKWBCSIUxVhVDLRqBGc1USntXuvDkK1XG1Nr00UP7Uh0fNPZlVy6a0kR5Ujsy307CHj3pzchyo0N2rQtdMb1t3VTJKqEJ_T1P-jD3Q3UElIDtmtcyqv3ovKC4oojzkWVqNkDVBq12VidzNLYdD4KeDcKSEw0N3EJfQhy8f3b_7NXv8bsmyN2ZaCNq-DaPlrXhTFID6D2LgRvmvtHxkjuvX73GnLvdTl4PYW9PP6g-6A7c5O_6IH47A</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1532987220</pqid></control><display><type>article</type><title>Mice lacking inositol 1,4,5-trisphosphate receptors exhibit dry eye</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><source>Public Library of Science (PLoS)</source><creator>Inaba, Takaaki ; Hisatsune, Chihiro ; Sasaki, Yasumasa ; Ogawa, Yoko ; Ebisui, Etsuko ; Ogawa, Naoko ; Matsui, Minoru ; Takeuchi, Tsutomu ; Mikoshiba, Katsuhiko ; Tsubota, Kazuo</creator><creatorcontrib>Inaba, Takaaki ; Hisatsune, Chihiro ; Sasaki, Yasumasa ; Ogawa, Yoko ; Ebisui, Etsuko ; Ogawa, Naoko ; Matsui, Minoru ; Takeuchi, Tsutomu ; Mikoshiba, Katsuhiko ; Tsubota, Kazuo</creatorcontrib><description>Tear secretion is important as it supplies water to the ocular surface and keeps eyes moist. Both the parasympathetic and sympathetic pathways contribute to tear secretion. Although intracellular Ca2+ elevation in the acinar cells of lacrimal glands is a crucial event for tear secretion in both the pathways, the Ca2+ channel, which is responsible for the Ca2+ elevation in the sympathetic pathway, has not been sufficiently analyzed. In this study, we examined tear secretion in mice lacking the inositol 1,4,5-trisphosphate receptor (IP3R) types 2 and 3 (Itpr2-/-;Itpr3-/-double-knockout mice). We found that tear secretion in both the parasympathetic and sympathetic pathways was abolished in Itpr2-/-;Itpr3-/- mice. Intracellular Ca2+ elevation in lacrimal acinar cells after acetylcholine and epinephrine stimulation was abolished in Itpr2-/-;Itpr3-/- mice. Consequently, Itpr2-/-;Itpr3-/- mice exhibited keratoconjunctival alteration and corneal epithelial barrier disruption. Inflammatory cell infiltration into the lacrimal glands and elevation of serum autoantibodies, a representative marker for Sjögren's syndrome (SS) in humans, were also detected in older Itpr2-/-;Itpr3-/- mice. These results suggested that IP3Rs are essential for tear secretion in both parasympathetic and sympathetic pathways and that Itpr2-/-;Itpr3-/- mice could be a new dry eye mouse model with symptoms that mimic those of SS.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0099205</identifier><identifier>PMID: 24901844</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acetylcholine ; Acetylcholine - pharmacology ; Acinar cells ; Acinar Cells - drug effects ; Acinar Cells - metabolism ; Analysis ; Animals ; Autoantibodies ; Autoantibodies - immunology ; Autoimmunity ; Biology and Life Sciences ; Brain research ; Calcium (intracellular) ; Calcium Signaling - drug effects ; Cornea ; Dry Eye Syndromes - metabolism ; Dry Eye Syndromes - pathology ; Dry Eye Syndromes - veterinary ; Epinephrine ; Epinephrine - pharmacology ; Epithelium, Corneal - metabolism ; Exhibitions ; Eye ; Eye (anatomy) ; Glands ; Histopathology ; Immunoglobulins ; Immunoglobulins - blood ; Infiltration ; Inflammation ; Inositol ; Inositol 1,4,5-trisphosphate receptors ; Inositol 1,4,5-Trisphosphate Receptors - deficiency ; Inositol 1,4,5-Trisphosphate Receptors - genetics ; Inositol 1,4,5-Trisphosphate Receptors - metabolism ; Intracellular ; Laboratory animals ; Lacrimal Apparatus - metabolism ; Lacrimal Apparatus - pathology ; Medicine ; Mice ; Mice, Knockout ; Neurobiology ; Neurosciences ; Parasympathetic nervous system ; Proteins ; Receptors ; Research and Analysis Methods ; Ribonucleoproteins - immunology ; Rodents ; Science ; Secretion ; Signal transduction ; Sjogren's syndrome ; Tearing ; Tears - metabolism</subject><ispartof>PloS one, 2014-06, Vol.9 (6), p.e99205-e99205</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Inaba et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Inaba et al 2014 Inaba et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-fb53dd67e649b702d1cb2901b23ca9c56add2fa7b6af7cdbae51453a1b90eaa43</citedby><cites>FETCH-LOGICAL-c758t-fb53dd67e649b702d1cb2901b23ca9c56add2fa7b6af7cdbae51453a1b90eaa43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047094/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047094/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24901844$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Inaba, Takaaki</creatorcontrib><creatorcontrib>Hisatsune, Chihiro</creatorcontrib><creatorcontrib>Sasaki, Yasumasa</creatorcontrib><creatorcontrib>Ogawa, Yoko</creatorcontrib><creatorcontrib>Ebisui, Etsuko</creatorcontrib><creatorcontrib>Ogawa, Naoko</creatorcontrib><creatorcontrib>Matsui, Minoru</creatorcontrib><creatorcontrib>Takeuchi, Tsutomu</creatorcontrib><creatorcontrib>Mikoshiba, Katsuhiko</creatorcontrib><creatorcontrib>Tsubota, Kazuo</creatorcontrib><title>Mice lacking inositol 1,4,5-trisphosphate receptors exhibit dry eye</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Tear secretion is important as it supplies water to the ocular surface and keeps eyes moist. Both the parasympathetic and sympathetic pathways contribute to tear secretion. Although intracellular Ca2+ elevation in the acinar cells of lacrimal glands is a crucial event for tear secretion in both the pathways, the Ca2+ channel, which is responsible for the Ca2+ elevation in the sympathetic pathway, has not been sufficiently analyzed. In this study, we examined tear secretion in mice lacking the inositol 1,4,5-trisphosphate receptor (IP3R) types 2 and 3 (Itpr2-/-;Itpr3-/-double-knockout mice). We found that tear secretion in both the parasympathetic and sympathetic pathways was abolished in Itpr2-/-;Itpr3-/- mice. Intracellular Ca2+ elevation in lacrimal acinar cells after acetylcholine and epinephrine stimulation was abolished in Itpr2-/-;Itpr3-/- mice. Consequently, Itpr2-/-;Itpr3-/- mice exhibited keratoconjunctival alteration and corneal epithelial barrier disruption. Inflammatory cell infiltration into the lacrimal glands and elevation of serum autoantibodies, a representative marker for Sjögren's syndrome (SS) in humans, were also detected in older Itpr2-/-;Itpr3-/- mice. These results suggested that IP3Rs are essential for tear secretion in both parasympathetic and sympathetic pathways and that Itpr2-/-;Itpr3-/- mice could be a new dry eye mouse model with symptoms that mimic those of SS.</description><subject>Acetylcholine</subject><subject>Acetylcholine - pharmacology</subject><subject>Acinar cells</subject><subject>Acinar Cells - drug effects</subject><subject>Acinar Cells - metabolism</subject><subject>Analysis</subject><subject>Animals</subject><subject>Autoantibodies</subject><subject>Autoantibodies - immunology</subject><subject>Autoimmunity</subject><subject>Biology and Life Sciences</subject><subject>Brain research</subject><subject>Calcium (intracellular)</subject><subject>Calcium Signaling - drug effects</subject><subject>Cornea</subject><subject>Dry Eye Syndromes - metabolism</subject><subject>Dry Eye Syndromes - pathology</subject><subject>Dry Eye Syndromes - veterinary</subject><subject>Epinephrine</subject><subject>Epinephrine - pharmacology</subject><subject>Epithelium, Corneal - metabolism</subject><subject>Exhibitions</subject><subject>Eye</subject><subject>Eye (anatomy)</subject><subject>Glands</subject><subject>Histopathology</subject><subject>Immunoglobulins</subject><subject>Immunoglobulins - blood</subject><subject>Infiltration</subject><subject>Inflammation</subject><subject>Inositol</subject><subject>Inositol 1,4,5-trisphosphate receptors</subject><subject>Inositol 1,4,5-Trisphosphate Receptors - deficiency</subject><subject>Inositol 1,4,5-Trisphosphate Receptors - genetics</subject><subject>Inositol 1,4,5-Trisphosphate Receptors - metabolism</subject><subject>Intracellular</subject><subject>Laboratory animals</subject><subject>Lacrimal Apparatus - metabolism</subject><subject>Lacrimal Apparatus - pathology</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Neurobiology</subject><subject>Neurosciences</subject><subject>Parasympathetic nervous system</subject><subject>Proteins</subject><subject>Receptors</subject><subject>Research and Analysis Methods</subject><subject>Ribonucleoproteins - immunology</subject><subject>Rodents</subject><subject>Science</subject><subject>Secretion</subject><subject>Signal transduction</subject><subject>Sjogren's syndrome</subject><subject>Tearing</subject><subject>Tears - metabolism</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl1r2zAUhs3YWNts_2BshsHYoMkkS7Ksm0EJ-wh0FPZ1K45kOVHmWJkkl-bfT2ncEo9eDCEkpOe85xzpzbIXGM0w4fj92vW-g3a2dZ2ZISREgdij7BQLUkzLApHHR_uT7CyENUKMVGX5NDspqEC4ovQ0m3-12uQt6N-2W-a2c8FG1-b4nJ6zafQ2bFcuTYgm90abbXQ-5OZmZZWNee13udmZZ9mTBtpgng_rJPv56eOP-Zfp5dXnxfzicqo5q-K0UYzUdclNSYXiqKixVkWqQxVEg9CshLouGuCqhIbrWoFhmDICWAlkACiZZK8OutvWBTn0HyRmpBAVL1Kfk2xxIGoHa7n1dgN-Jx1YeXvg_FKCj1a3RjLWEKWBCSIUxVhVDLRqBGc1USntXuvDkK1XG1Nr00UP7Uh0fNPZlVy6a0kR5Ujsy307CHj3pzchyo0N2rQtdMb1t3VTJKqEJ_T1P-jD3Q3UElIDtmtcyqv3ovKC4oojzkWVqNkDVBq12VidzNLYdD4KeDcKSEw0N3EJfQhy8f3b_7NXv8bsmyN2ZaCNq-DaPlrXhTFID6D2LgRvmvtHxkjuvX73GnLvdTl4PYW9PP6g-6A7c5O_6IH47A</recordid><startdate>20140605</startdate><enddate>20140605</enddate><creator>Inaba, Takaaki</creator><creator>Hisatsune, Chihiro</creator><creator>Sasaki, Yasumasa</creator><creator>Ogawa, Yoko</creator><creator>Ebisui, Etsuko</creator><creator>Ogawa, Naoko</creator><creator>Matsui, Minoru</creator><creator>Takeuchi, Tsutomu</creator><creator>Mikoshiba, Katsuhiko</creator><creator>Tsubota, Kazuo</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20140605</creationdate><title>Mice lacking inositol 1,4,5-trisphosphate receptors exhibit dry eye</title><author>Inaba, Takaaki ; Hisatsune, Chihiro ; Sasaki, Yasumasa ; Ogawa, Yoko ; Ebisui, Etsuko ; Ogawa, Naoko ; Matsui, Minoru ; Takeuchi, Tsutomu ; Mikoshiba, Katsuhiko ; Tsubota, Kazuo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-fb53dd67e649b702d1cb2901b23ca9c56add2fa7b6af7cdbae51453a1b90eaa43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Acetylcholine</topic><topic>Acetylcholine - pharmacology</topic><topic>Acinar cells</topic><topic>Acinar Cells - drug effects</topic><topic>Acinar Cells - metabolism</topic><topic>Analysis</topic><topic>Animals</topic><topic>Autoantibodies</topic><topic>Autoantibodies - immunology</topic><topic>Autoimmunity</topic><topic>Biology and Life Sciences</topic><topic>Brain research</topic><topic>Calcium (intracellular)</topic><topic>Calcium Signaling - drug effects</topic><topic>Cornea</topic><topic>Dry Eye Syndromes - metabolism</topic><topic>Dry Eye Syndromes - pathology</topic><topic>Dry Eye Syndromes - veterinary</topic><topic>Epinephrine</topic><topic>Epinephrine - pharmacology</topic><topic>Epithelium, Corneal - metabolism</topic><topic>Exhibitions</topic><topic>Eye</topic><topic>Eye (anatomy)</topic><topic>Glands</topic><topic>Histopathology</topic><topic>Immunoglobulins</topic><topic>Immunoglobulins - blood</topic><topic>Infiltration</topic><topic>Inflammation</topic><topic>Inositol</topic><topic>Inositol 1,4,5-trisphosphate receptors</topic><topic>Inositol 1,4,5-Trisphosphate Receptors - deficiency</topic><topic>Inositol 1,4,5-Trisphosphate Receptors - genetics</topic><topic>Inositol 1,4,5-Trisphosphate Receptors - metabolism</topic><topic>Intracellular</topic><topic>Laboratory animals</topic><topic>Lacrimal Apparatus - metabolism</topic><topic>Lacrimal Apparatus - pathology</topic><topic>Medicine</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Neurobiology</topic><topic>Neurosciences</topic><topic>Parasympathetic nervous system</topic><topic>Proteins</topic><topic>Receptors</topic><topic>Research and Analysis Methods</topic><topic>Ribonucleoproteins - immunology</topic><topic>Rodents</topic><topic>Science</topic><topic>Secretion</topic><topic>Signal transduction</topic><topic>Sjogren's syndrome</topic><topic>Tearing</topic><topic>Tears - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Inaba, Takaaki</creatorcontrib><creatorcontrib>Hisatsune, Chihiro</creatorcontrib><creatorcontrib>Sasaki, Yasumasa</creatorcontrib><creatorcontrib>Ogawa, Yoko</creatorcontrib><creatorcontrib>Ebisui, Etsuko</creatorcontrib><creatorcontrib>Ogawa, Naoko</creatorcontrib><creatorcontrib>Matsui, Minoru</creatorcontrib><creatorcontrib>Takeuchi, Tsutomu</creatorcontrib><creatorcontrib>Mikoshiba, Katsuhiko</creatorcontrib><creatorcontrib>Tsubota, Kazuo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Inaba, Takaaki</au><au>Hisatsune, Chihiro</au><au>Sasaki, Yasumasa</au><au>Ogawa, Yoko</au><au>Ebisui, Etsuko</au><au>Ogawa, Naoko</au><au>Matsui, Minoru</au><au>Takeuchi, Tsutomu</au><au>Mikoshiba, Katsuhiko</au><au>Tsubota, Kazuo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mice lacking inositol 1,4,5-trisphosphate receptors exhibit dry eye</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-06-05</date><risdate>2014</risdate><volume>9</volume><issue>6</issue><spage>e99205</spage><epage>e99205</epage><pages>e99205-e99205</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Tear secretion is important as it supplies water to the ocular surface and keeps eyes moist. Both the parasympathetic and sympathetic pathways contribute to tear secretion. Although intracellular Ca2+ elevation in the acinar cells of lacrimal glands is a crucial event for tear secretion in both the pathways, the Ca2+ channel, which is responsible for the Ca2+ elevation in the sympathetic pathway, has not been sufficiently analyzed. In this study, we examined tear secretion in mice lacking the inositol 1,4,5-trisphosphate receptor (IP3R) types 2 and 3 (Itpr2-/-;Itpr3-/-double-knockout mice). We found that tear secretion in both the parasympathetic and sympathetic pathways was abolished in Itpr2-/-;Itpr3-/- mice. Intracellular Ca2+ elevation in lacrimal acinar cells after acetylcholine and epinephrine stimulation was abolished in Itpr2-/-;Itpr3-/- mice. Consequently, Itpr2-/-;Itpr3-/- mice exhibited keratoconjunctival alteration and corneal epithelial barrier disruption. Inflammatory cell infiltration into the lacrimal glands and elevation of serum autoantibodies, a representative marker for Sjögren's syndrome (SS) in humans, were also detected in older Itpr2-/-;Itpr3-/- mice. These results suggested that IP3Rs are essential for tear secretion in both parasympathetic and sympathetic pathways and that Itpr2-/-;Itpr3-/- mice could be a new dry eye mouse model with symptoms that mimic those of SS.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24901844</pmid><doi>10.1371/journal.pone.0099205</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-06, Vol.9 (6), p.e99205-e99205 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1532987220 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Acetylcholine Acetylcholine - pharmacology Acinar cells Acinar Cells - drug effects Acinar Cells - metabolism Analysis Animals Autoantibodies Autoantibodies - immunology Autoimmunity Biology and Life Sciences Brain research Calcium (intracellular) Calcium Signaling - drug effects Cornea Dry Eye Syndromes - metabolism Dry Eye Syndromes - pathology Dry Eye Syndromes - veterinary Epinephrine Epinephrine - pharmacology Epithelium, Corneal - metabolism Exhibitions Eye Eye (anatomy) Glands Histopathology Immunoglobulins Immunoglobulins - blood Infiltration Inflammation Inositol Inositol 1,4,5-trisphosphate receptors Inositol 1,4,5-Trisphosphate Receptors - deficiency Inositol 1,4,5-Trisphosphate Receptors - genetics Inositol 1,4,5-Trisphosphate Receptors - metabolism Intracellular Laboratory animals Lacrimal Apparatus - metabolism Lacrimal Apparatus - pathology Medicine Mice Mice, Knockout Neurobiology Neurosciences Parasympathetic nervous system Proteins Receptors Research and Analysis Methods Ribonucleoproteins - immunology Rodents Science Secretion Signal transduction Sjogren's syndrome Tearing Tears - metabolism |
| title | Mice lacking inositol 1,4,5-trisphosphate receptors exhibit dry eye |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T13%3A43%3A52IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Mice%20lacking%20inositol%201,4,5-trisphosphate%20receptors%20exhibit%20dry%20eye&rft.jtitle=PloS%20one&rft.au=Inaba,%20Takaaki&rft.date=2014-06-05&rft.volume=9&rft.issue=6&rft.spage=e99205&rft.epage=e99205&rft.pages=e99205-e99205&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0099205&rft_dat=%3Cgale_plos_%3EA418707798%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1532987220&rft_id=info:pmid/24901844&rft_galeid=A418707798&rft_doaj_id=oai_doaj_org_article_55f3bca5939b411b85acbf975d3b1450&rfr_iscdi=true |