{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:18:19Z","timestamp":1790403499339,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,5,4]],"date-time":"2015-05-04T00:00:00Z","timestamp":1430697600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Ministry of science and technology","award":["MOST103-2321-B-001-037"],"award-info":[{"award-number":["MOST103-2321-B-001-037"]}]},{"name":"Ministry of science and technology","award":["MOST-103-2325-B-001-015"],"award-info":[{"award-number":["MOST-103-2325-B-001-015"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J of Neuroscience"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Although <jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>4 is a member of the acid\u2010sensing ion channel (<jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>) family, we have limited knowledge of its expression and physiological function <jats:italic>in\u00a0vivo<\/jats:italic>. To trace the expression of this ion channel, we generated the <jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>4\u2010knockout\/Cre<jats:styled-content style=\"fixed-case\">ERT<\/jats:styled-content><jats:sup>2<\/jats:sup>\u2010knockin (<jats:italic>Asic4<\/jats:italic><jats:sup><jats:italic>Cre<\/jats:italic><\/jats:sup><jats:styled-content style=\"fixed-case\"><jats:sup><jats:italic>ERT<\/jats:italic><\/jats:sup><\/jats:styled-content><jats:sup><jats:italic>2<\/jats:italic><\/jats:sup>) mouse line. After tamoxifen induction in the <jats:italic>Asic4<\/jats:italic><jats:sup><jats:italic>Cre<\/jats:italic><\/jats:sup><jats:styled-content style=\"fixed-case\"><jats:sup><jats:italic>ERT<\/jats:italic><\/jats:sup><\/jats:styled-content><jats:sup><jats:italic>2<\/jats:italic><\/jats:sup>::<jats:styled-content style=\"fixed-case\">CAG<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">STOP<\/jats:styled-content><jats:sup>floxed<\/jats:sup>\u2010Td\u2010tomato double transgenic mice, we mapped the expression of <jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>4 at the cellular level in the central nervous system (<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>). <jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>4 was expressed in many brain regions, including the olfactory bulb, cerebral cortex, striatum, hippocampus, amygdala, thalamus, hypothalamus, brain stem, cerebellum, spinal cord and pituitary gland. Colocalisation studies further revealed that <jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>4 was expressed mainly in three types of cells in the <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>: (i) calretinin (<jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>)\u2010positive and\/or vasoactive intestine peptide (<jats:styled-content style=\"fixed-case\">VIP<\/jats:styled-content>)\u2010positive interneurons; (ii) neural\/glial antigen\u00a02 (<jats:styled-content style=\"fixed-case\">NG<\/jats:styled-content>2)\u2010positive glia, also known as oligodendrocyte precursor cells; and (iii) cerebellar granule cells. To probe the possible role of <jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>4, we hypothesised that <jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>4 could modulate the membrane expression of <jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>1a and thus <jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>1a signaling <jats:italic>in\u00a0vivo<\/jats:italic>. We conducted behavioral phenotyping of <jats:italic>Asic4<\/jats:italic><jats:sup><jats:italic>Cre<\/jats:italic><\/jats:sup><jats:styled-content style=\"fixed-case\"><jats:sup><jats:italic>ERT<\/jats:italic><\/jats:sup><\/jats:styled-content><jats:sup><jats:italic>2<\/jats:italic><\/jats:sup> mice by screening many of the known behavioral phenotypes found in <jats:italic>Asic1a<\/jats:italic> knockouts and found <jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>4 not involved in shock\u2010evoked fear learning and memory, seizure termination or psychostimulant\u2010induced locomotion\/rewarding effects. In contrast, <jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>4 might play an important role in modulating the innate fear response to predator odor and anxious state because <jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>4\u2010mutant mice showed increased freezing response to 2,4,5\u2010trimethylthiazoline and elevated anxiety\u2010like behavior in both the open\u2010field and elevated\u2010plus maze. <jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>4 may modulate fear and anxiety by counteracting <jats:styled-content style=\"fixed-case\">ASIC<\/jats:styled-content>1a activity in the brain.<\/jats:p>","DOI":"10.1111\/ejn.12905","type":"journal-article","created":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T15:21:47Z","timestamp":1427901707000},"page":"1553-1568","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Genetic mapping of <scp>ASIC<\/scp>4 and contrasting phenotype to <scp>ASIC<\/scp>1a in modulating innate fear and anxiety"],"prefix":"10.1111","volume":"41","author":[{"given":"Shing\u2010Hong","family":"Lin","sequence":"first","affiliation":[{"name":"Graduate institute of Life Sciences National Defense Medical Center Taipei Taiwan"},{"name":"Institute of Biomedical Sciences Academia Sinica Taipei 115 Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Chih","family":"Chien","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences Academia Sinica Taipei 115 Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Wei","family":"Chiang","sequence":"additional","affiliation":[{"name":"Taiwan Mouse Clinic\u2010National Comprehensive Mouse Phenotyping and Drug Testing Center Academia Sinica Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan\u2010Zhen","family":"Liu","sequence":"additional","affiliation":[{"name":"Taiwan Mouse Clinic\u2010National Comprehensive Mouse Phenotyping and Drug Testing Center Academia Sinica Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng\u2010Chang","family":"Lien","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience National Yang\u2010Ming University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih\u2010Cheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate institute of Life Sciences National Defense Medical Center Taipei Taiwan"},{"name":"Institute of Biomedical Sciences Academia Sinica Taipei 115 Taiwan"},{"name":"Taiwan Mouse Clinic\u2010National Comprehensive Mouse Phenotyping and Drug Testing Center Academia Sinica Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,5,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2014.12.012"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200007140-00031"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.042688199"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.030692"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2013.06.034"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2015.01.005"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1324060111"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2014.00052"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3043-13.2013"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12025"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2007.05.008"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3907-08.2008"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5420.1670"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2004.09.020"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2008.06282.x"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0115310"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003643200"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.7124"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20693"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.03.023"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0752-09.2009"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200006050-00003"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2014.12.009"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2014.12.010"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06163"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2013.04.059"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5021-11.2012"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1149381"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3750"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2014.12.014"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012665"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2014.12.011"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(01)00086-9"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2007.05.021"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2014.12.007"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/gbb.12108"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2008.05.006"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2004.12.009"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00188.2012"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2014.12.013"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0039982"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2014.00072"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00661-X"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-13-05496.2003"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0582-10.2010"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1954"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-183X.2010.00591.x"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2011.12.009"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4132-12.2013"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22229"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5206-12.2013"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2132"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.10.029"}],"container-title":["European Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fejn.12905","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ejn.12905","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T14:52:40Z","timestamp":1696344760000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ejn.12905"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5,4]]},"references-count":53,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2015,6]]}},"alternative-id":["10.1111\/ejn.12905"],"URL":"https:\/\/doi.org\/10.1111\/ejn.12905","archive":["Portico"],"relation":{},"ISSN":["0953-816X","1460-9568"],"issn-type":[{"value":"0953-816X","type":"print"},{"value":"1460-9568","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5,4]]},"assertion":[{"value":"2015-02-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-03-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-05-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}