{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:44:46Z","timestamp":1789659886695,"version":"4.0.1"},"reference-count":45,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Physiological Genomics"],"published-print":{"date-parts":[[2007,5]]},"abstract":"<jats:p>For most vertebrates, oxygen is a prerequisite for survival. Although we have previously shown that Drosophila melanogaster is hypoxia tolerant, how this species senses O<jats:sub>2<\/jats:sub>deprivation and how it survives oxygen-limiting conditions are as yet poorly understood. We began to address this question by testing for anoxic responsiveness in Drosophila adult flies following overexpression of existing EP lines. In this screen, we identified Drosophila CG14709 gene as a homolog of the human multidrug resistance protein 4 (MRP4\/ABCC4) that is tightly regulated to oxygen. Ubiquitous expression of dMRP4 in adult flies resulted in increased sensitivity to anoxia as they had longer recovery time from anoxic stupor. When exposed to 4% oxygen chronically (throughout its lifespan), constitutive expression of dMRP4 in larvae caused larval lethality due to growth arrest. Mutations of dMRP4 led to a hypersensitive response to acute anoxia in adult flies but had less impact on larval survival under chronic hypoxia compared with dMRP4 overexpression. Selective expression of this gene in neurons, but not in glia or muscles, mirrored the same phenotype as the ubiquitous one. Thus, our data suggest novel roles for MRP in vivo: 1) dMRP4 regulates the sensitivity to acute or chronic O<jats:sub>2<\/jats:sub>deprivation, and 2) dMRP expression in neurons is sufficient to induce the sensitivity to O<jats:sub>2<\/jats:sub>in the whole organism.<\/jats:p>","DOI":"10.1152\/physiolgenomics.00166.2006","type":"journal-article","created":{"date-parts":[[2007,2,7]],"date-time":"2007-02-07T08:58:56Z","timestamp":1170838736000},"page":"260-266","source":"Crossref","is-referenced-by-count":18,"title":["<i>Drosophila dMRP4<\/i>regulates responsiveness to O<sub>2<\/sub>deprivation and development under hypoxia"],"prefix":"10.1152","volume":"29","author":[{"given":"He","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of California San Diego and the Rady Children's Hospital of San Diego, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel G.","family":"Haddad","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Diego and the Rady Children's Hospital of San Diego, La Jolla, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2004.04.001"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9234"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1177\/1073858402008003009"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-3806(97)00189-2"},{"key":"R5","doi-asserted-by":"crossref","unstructured":"Brand AH, Perrimon N.Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.Development118: 401\u2013415, 1993.","DOI":"10.1242\/dev.118.2.401"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbrainres.2004.08.013"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.6.080604.162122"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1101\/gr.GR-1649R"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003911200"},{"key":"R10","doi-asserted-by":"crossref","unstructured":"Donohoe PH, West TG, Boutilier RG.Factors affecting membrane permeability and ionic homeostasis in the cold-submerged frog.J Exp Biol203: 405\u2013414, 2000.","DOI":"10.1242\/jeb.203.2.405"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1038\/35041687"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1046\/j.1525-1373.1999.d01-140.x"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1243304"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinsphys.2006.01.002"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2000.88.4.1481"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2005.030767"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1990.sp018265"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)91067-3"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.20.10809"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(01)00124-5"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1910(96)00084-4"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.19.6842-6853.2002"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(00)00340-7"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(94)90022-1"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00262.2005"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1985.249.3.R372"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1172\/JCI11625"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(98)00265-4"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1002\/gene.10130"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(98)00147-6"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1990.258.6.R1308"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)00049-0"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1124\/mol.63.5.1094"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.22.12418"},{"key":"R35","doi-asserted-by":"crossref","unstructured":"Rorth P, Szabo K, Bailey A, Laverty T, Rehm J, Rubin GM, Weigmann K, Milan M, Benes V, Ansorge W, Cohen SM.Systematic gain-of-function genetics in Drosophila.Development125: 1049\u20131057, 1998.","DOI":"10.1242\/dev.125.6.1049"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(02)00169-2"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80891-0"},{"key":"R38","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2004-5-3-r15"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1982.243.3.R281"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1111\/j.0962-1075.2004.00512.x"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00027.2002"},{"key":"R42","doi-asserted-by":"crossref","unstructured":"Ultsch GR, Jackson DC.Long-term submergence at 3 degrees C of the turtle Chrysemys picta bellii in normoxic and severely hypoxic water. III. Effects of changes in ambient PO2 and subsequent air breathing.J Exp Biol97: 87\u201399, 1982.","DOI":"10.1242\/jeb.97.1.87"},{"key":"R43","unstructured":"Val AL.Oxygen transfer in fish: morphological and molecular adjustments.Braz J Med Biol Res28: 1119\u20131127, 1995."},{"key":"R44","unstructured":"Van Aubel RA, Smeets PH, Peters JG, Bindels RJ, Russel FG.The MRP4\/ABCC4 gene encodes a novel apical organic anion transporter in human kidney proximal tubules: putative efflux pump for urinary cAMP and cGMP.J Am Soc Nephrol13: 595\u2013603, 2002."},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80610-8"}],"container-title":["Physiological Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/physiolgenomics.00166.2006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,8]],"date-time":"2021-08-08T13:01:19Z","timestamp":1628427679000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/physiolgenomics.00166.2006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,5]]},"references-count":45,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2007,5]]}},"alternative-id":["10.1152\/physiolgenomics.00166.2006"],"URL":"https:\/\/doi.org\/10.1152\/physiolgenomics.00166.2006","relation":{},"ISSN":["1094-8341","1531-2267"],"issn-type":[{"value":"1094-8341","type":"print"},{"value":"1531-2267","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,5]]}}}