{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T11:16:26Z","timestamp":1784718986694,"version":"3.55.0"},"reference-count":46,"publisher":"The Company of Biologists","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,4,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Ecological studies show that mice can be found at high altitude (HA \u2013 up to 4000\u2005m) while rats are absent at these altitudes, and there are no data to explain this discrepancy. We used adult laboratory rats and mice that have been raised for more than 30 generations in La Paz, Bolivia (3600\u2005m), and compared their hematocrit levels, right ventricular hypertrophy (index of pulmonary hypertension) and alveolar surface area in the lungs. We also used whole-body plethysmography, indirect calorimetry and pulse oxymetry to measure ventilation, metabolic rate (O2 consumption and CO2 production), heart rate and pulse oxymetry oxygen saturation (pO2,sat) under ambient conditions, and in response to exposure to sea level PO2\u00a0(32% O2=160\u2005mmHg for 10\u2005min) and hypoxia (18% and 15% O2=90 and 75\u2005mmHg for 10\u2005min each). The variables used for comparisons between species were corrected for body mass using standard allometric equations, and are termed mass-corrected variables. Under baseline, compared with rats, adult mice had similar levels of pO2,sat, but lower hematocrit and hemoglobin levels, reduced right ventricular hypertrophy and higher mass-corrected alveolar surface area, tidal volume and metabolic rate. In response to sea level PO2\u00a0and hypoxia, mice and rats had similar changes of ventilation, but metabolic rate decreased much more in hypoxia in mice, while pO2,sat remained higher in mice. We conclude that laboratory mice and rats that have been raised at HA for &amp;gt;30 generations have different physiological responses to altitude. These differences might explain the different altitude distribution observed in wild rats and mice.<\/jats:p>","DOI":"10.1242\/jeb.112862","type":"journal-article","created":{"date-parts":[[2015,2,6]],"date-time":"2015-02-06T03:56:58Z","timestamp":1423195018000},"page":"1035-1043","source":"Crossref","is-referenced-by-count":38,"title":["Divergent physiological responses in laboratory rats and mice raised at high altitude"],"prefix":"10.1242","volume":"218","author":[{"given":"Alexandra","family":"Jochmans-Lemoine","sequence":"first","affiliation":[{"name":"Centre de Recherche du CHU de Qu\u00e9bec, and Universit\u00e9 Laval, Quebec, Quebec, Canada\u2008G1L3L5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Villalpando","sequence":"additional","affiliation":[{"name":"Instituto Boliviano de Biologia de Altura, and Universidad Mayor de San Andr\u00e9s, La Paz, Bolivia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelino","family":"Gonzales","sequence":"additional","affiliation":[{"name":"Instituto Boliviano de Biologia de Altura, and Universidad Mayor de San Andr\u00e9s, La Paz, Bolivia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibana","family":"Valverde","sequence":"additional","affiliation":[{"name":"Instituto Boliviano de Biologia de Altura, and Universidad Mayor de San Andr\u00e9s, La Paz, Bolivia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudy","family":"Soria","sequence":"additional","affiliation":[{"name":"Instituto Boliviano de Biologia de Altura, and Universidad Mayor de San Andr\u00e9s, La Paz, Bolivia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Joseph","sequence":"additional","affiliation":[{"name":"Centre de Recherche du CHU de Qu\u00e9bec, and Universit\u00e9 Laval, Quebec, Quebec, Canada\u2008G1L3L5"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021052800123848600_JEB112862C1","article-title":"Mammals of Bolivia: Taxonomy and Distribution. Bulletin of the American Museum of Natural History no. 231","author":"Anderson","year":"1997"},{"key":"2021052800123848600_JEB112862C2","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1152\/jappl.2001.91.2.603","article-title":"Hypoxic metabolic response of the golden-mantled ground squirrel","volume":"91","author":"Barros","year":"2001","journal-title":"J. Appl. Physiol."},{"key":"2021052800123848600_JEB112862C3","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1016\/0034-5687(70)90056-3","article-title":"Control of breathing in experimental anemia","volume":"10","author":"Bartlett","year":"1970","journal-title":"Respir. Physiol."},{"key":"2021052800123848600_JEB112862C4","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1146\/annurev.physiol.69.031905.162529","article-title":"Hypoxia tolerance in reptiles, amphibians, and fishes: life with variable oxygen availability","volume":"69","author":"Bickler","year":"2007","journal-title":"Annu. Rev. Physiol."},{"key":"2021052800123848600_JEB112862C5","doi-asserted-by":"publisher","first-page":"8635","DOI":"10.1073\/pnas.1120523109","article-title":"Regulatory changes contribute to the adaptive enhancement of thermogenic capacity in high-altitude deer mice","volume":"109","author":"Cheviron","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021052800123848600_JEB112862C6","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1164\/rccm.201103-0412OC","article-title":"A novel murine model of severe pulmonary arterial hypertension","volume":"184","author":"Ciuclan","year":"2011","journal-title":"Am. J. Respir. Crit. Care. Med."},{"key":"2021052800123848600_JEB112862C7","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1152\/japplphysiol.01126.2013","article-title":"Role of chemoreception in cardiorespiratory acclimatization to, and deacclimatization from, hypoxia","volume":"116","author":"Dempsey","year":"2014","journal-title":"J. Appl. Physiol."},{"key":"2021052800123848600_JEB112862C8","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1053\/ajkd.2001.26111","article-title":"Why is erythropoietin made in the kidney? The kidney functions as a critmeter","volume":"38","author":"Donnelly","year":"2001","journal-title":"Am. J. Kidney Dis."},{"key":"2021052800123848600_JEB112862C9","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1182\/blood-2013-01-478065","article-title":"Erythrocytosis: the HIF pathway in control","volume":"122","author":"Franke","year":"2013","journal-title":"Blood"},{"key":"2021052800123848600_JEB112862C10","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1086\/physzool.67.4.30163866","article-title":"Why not to do two-species comparative studies: limitations on inferring adaptation","volume":"67","author":"Garland","year":"1994","journal-title":"Physiol. Zool."},{"key":"2021052800123848600_JEB112862C11","first-page":"1","volume-title":"Clinical Laboratory Parameters for Crl: CD (SD) Rats","author":"Giknis","year":"2006"},{"key":"2021052800123848600_JEB112862C12","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1093\/oso\/9780195117028.003.0002","article-title":"Cellular mechanism, regulation, and homeostasis","volume-title":"Biochemical Adaptation: Mechanism and Process in Physiological Evolution","author":"Hochachka","year":"2002"},{"key":"2021052800123848600_JEB112862C13","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1164\/rccm.200809-1522ST","article-title":"An official research policy statement of the American Thoracic Society\/European Respiratory Society: standards for quantitative assessment of lung structure","volume":"181","author":"Hsia","year":"2010","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2021052800123848600_JEB112862C14","first-page":"174","article-title":"Norway rat - ship rat","volume-title":"The Handbook of New Zealand Mammals","author":"Innes","year":"2005"},{"key":"2021052800123848600_JEB112862C15","doi-asserted-by":"publisher","first-page":"3565","DOI":"10.1007\/s00018-009-0143-y","article-title":"Breathing at high altitude","volume":"66","author":"Joseph","year":"2009","journal-title":"Cell. Mol. Life Sci."},{"key":"2021052800123848600_JEB112862C16","first-page":"R765","article-title":"Dopaminergic metabolism in carotid bodies and high altitude acclimatization in female rats","volume":"282","author":"Joseph","year":"2002","journal-title":"Am. J. Physiol."},{"key":"2021052800123848600_JEB112862C17","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1073\/pnas.022634199","article-title":"Defective carotid body function and impaired ventilatory responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1 alpha","volume":"99","author":"Kline","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021052800123848600_JEB112862C18","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1161\/01.HYP.22.1.97","article-title":"Circadian blood pressure variation in transgenic hypertensive rats","volume":"22","author":"Lemmer","year":"1993","journal-title":"Hypertension"},{"key":"2021052800123848600_JEB112862C19","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1093\/acprof:oso\/9780195310610.003.0010","article-title":"Flow-through respirometry using incurrent flow measurments","volume-title":"Measuring Metabolic Rate: A Manual for Scientists","author":"Lighton","year":"2008"},{"key":"2021052800123848600_JEB112862C20","doi-asserted-by":"publisher","first-page":"R421","DOI":"10.1152\/ajpregu.00068.2009","article-title":"Impaired acclimatization to chronic hypoxia in adult male and female rats following neonatal hypoxia","volume":"297","author":"Lumbroso","year":"2009","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2021052800123848600_JEB112862C21","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1152\/japplphysiol.01043.2011","article-title":"Life-long consequences of postnatal normoxia exposure in rats raised at high altitude","volume":"112","author":"Lumbroso","year":"2012","journal-title":"J. Appl. Physiol."},{"key":"2021052800123848600_JEB112862C22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1098\/rstb.1989.0104","article-title":"An allometric study of pulmonary morphometric parameters in birds, with mammalian comparisons","volume":"326","author":"Maina","year":"1989","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"2021052800123848600_JEB112862C23","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1152\/physrev.1991.71.4.1135","article-title":"Physiological adaptation to high altitude: oxygen transport in mammals and birds","volume":"71","author":"Monge","year":"1991","journal-title":"Physiol. Rev."},{"key":"2021052800123848600_JEB112862C24","doi-asserted-by":"publisher","first-page":"R496","DOI":"10.1152\/ajpregu.00573.2001","article-title":"17Beta-estradiol decreases hypoxic induction of erythropoietin gene expression","volume":"283","author":"Mukundan","year":"2002","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2021052800123848600_JEB112862C25","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1183\/09059180.00007414","article-title":"The right ventricle in pulmonary arterial hypertension","volume":"23","author":"Naeije","year":"2014","journal-title":"Eur. Respir. Rev."},{"key":"2021052800123848600_JEB112862C26","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/j.ijdevneu.2012.04.004","article-title":"Effect of hypoxia on metabolic rate, core body temperature, and c-fos expression in the naked mole rat","volume":"30","author":"Nathaniel","year":"2012","journal-title":"Int. J. Dev. Neurosci."},{"key":"2021052800123848600_JEB112862C27","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.1113\/jphysiol.2010.194241","article-title":"Erythropoietin down-regulates proximal renal tubular reabsorption and causes a fall in glomerular filtration rate in humans","volume":"589","author":"Olsen","year":"2011","journal-title":"J. Physiol."},{"key":"2021052800123848600_JEB112862C28","doi-asserted-by":"publisher","first-page":"1981","DOI":"10.1046\/j.0953-816x.2001.01816.x","article-title":"Selective cardiorespiratory and catecholaminergic areas express the hypoxia-inducible factor-1alpha (HIF-1alpha) under in vivo hypoxia in rat brainstem","volume":"14","author":"Pascual","year":"2001","journal-title":"Eur. J. Neurosci."},{"key":"2021052800123848600_JEB112862C29","doi-asserted-by":"publisher","first-page":"e00032","DOI":"10.1002\/phy2.32","article-title":"Cardiac adaptation to high altitude in the plateau pika (Ochotona curzoniae)","volume":"1","author":"Pichon","year":"2013","journal-title":"Physiol. Rep."},{"key":"2021052800123848600_JEB112862C30","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.resp.2008.07.017","article-title":"HIF-1 and ventilatory acclimatization to chronic hypoxia","volume":"164","author":"Powell","year":"2008","journal-title":"Respir. Physiol. Neurobiol."},{"key":"2021052800123848600_JEB112862C31","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1152\/physrev.00030.2011","article-title":"Adaptive and maladaptive cardiorespiratory responses to continuous and intermittent hypoxia mediated by hypoxia-inducible factors 1 and 2","volume":"92","author":"Prabhakar","year":"2012","journal-title":"Physiol. Rev."},{"key":"2021052800123848600_JEB112862C32","first-page":"348","article-title":"[Hypoxic adaptation of the hearts of plateau zokor (Myospalax baileyi) and plateau pika (Ochotona curzoniae)]","volume":"60","author":"Qi","year":"2008","journal-title":"Sheng Li Xue Bao"},{"key":"2021052800123848600_JEB112862C33","doi-asserted-by":"publisher","first-page":"R435","DOI":"10.1152\/ajpregu.00037.2013","article-title":"The in vivo regulation of heart rate in the murine sinoatrial node by stimulatory and inhibitory heterotrimeric G proteins","volume":"305","author":"Sebastian","year":"2013","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2021052800123848600_JEB112862C34","volume-title":"The Laboratory Rat","author":"Sharp","year":"1998"},{"key":"2021052800123848600_JEB112862C35","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1113\/jphysiol.2007.133454","article-title":"Soluble erythropoietin receptor is present in the mouse brain and is required for the ventilatory acclimatization to hypoxia","volume":"583","author":"Soliz","year":"2007","journal-title":"J. Physiol."},{"key":"2021052800123848600_JEB112862C36","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1152\/jappl.1967.22.3.453","article-title":"Scaling of respiratory variables in mammals","volume":"22","author":"Stahl","year":"1967","journal-title":"J. Appl. Physiol."},{"key":"2021052800123848600_JEB112862C37","doi-asserted-by":"publisher","first-page":"R1412","DOI":"10.1152\/ajpregu.00328.2002","article-title":"A neurochemical mechanism for hypoxia-induced anapyrexia","volume":"283","author":"Steiner","year":"2002","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2021052800123848600_JEB112862C38","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1534\/genetics.107.078550","article-title":"Complex signatures of selection and gene conversion in the duplicated globin genes of house mice","volume":"177","author":"Storz","year":"2007","journal-title":"Genetics"},{"key":"2021052800123848600_JEB112862C39","doi-asserted-by":"publisher","first-page":"14450","DOI":"10.1073\/pnas.0905224106","article-title":"Evolutionary and functional insights into the mechanism underlying high-altitude adaptation of deer mouse hemoglobin","volume":"106","author":"Storz","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021052800123848600_JEB112862C40","doi-asserted-by":"publisher","first-page":"2565","DOI":"10.1242\/jeb.042598","article-title":"Genetic differences in hemoglobin function between highland and lowland deer mice","volume":"213","author":"Storz","year":"2010","journal-title":"J. Exp. Biol."},{"key":"2021052800123848600_JEB112862C41","doi-asserted-by":"publisher","first-page":"4125","DOI":"10.1242\/jeb.048181","article-title":"Phenotypic plasticity and genetic adaptation to high-altitude hypoxia in vertebrates","volume":"213","author":"Storz","year":"2010","journal-title":"J. Exp. Biol."},{"key":"2021052800123848600_JEB112862C42","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1038\/197054a0","article-title":"Comparative quantitative morphology of the mammalian lung: diffusing area","volume":"197","author":"Tenney","year":"1963","journal-title":"Nature"},{"key":"2021052800123848600_JEB112862C43","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1089\/152702901750265288","article-title":"Role of vascular smooth muscle in the development of high altitude pulmonary hypertension: an interspecies evaluation","volume":"2","author":"Tucker","year":"2001","journal-title":"High Alt. Med. Biol."},{"key":"2021052800123848600_JEB112862C44","doi-asserted-by":"publisher","first-page":"7676","DOI":"10.1073\/pnas.0801507105","article-title":"Dating the late prehistoric dispersal of Polynesians to New Zealand using the commensal Pacific rat","volume":"105","author":"Wilmshurst","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2021052800123848600_JEB112862C45","doi-asserted-by":"crossref","DOI":"10.56021\/9780801882210","volume-title":"Mammal Species of the World: A Taxonomic and Geographic Reference","author":"Wilson","year":"2005","edition":"3rd edn"},{"key":"2021052800123848600_JEB112862C46","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1038\/ng.847","article-title":"Subspecific origin and haplotype diversity in the laboratory mouse","volume":"43","author":"Yang","year":"2011","journal-title":"Nat. Genet."}],"container-title":["Journal of Experimental Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.biologists.com\/jeb\/article-pdf\/218\/7\/1035\/2076085\/jeb112862.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/jeb\/article-pdf\/doi\/10.1242\/jeb.112862\/2033126\/jeb_112862.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/jeb\/article-pdf\/218\/7\/1035\/2076085\/jeb112862.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T01:43:23Z","timestamp":1717724603000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jeb\/article\/218\/7\/1035\/14532\/Divergent-physiological-responses-in-laboratory"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,4,1]]},"references-count":46,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2015,4,1]]}},"URL":"https:\/\/doi.org\/10.1242\/jeb.112862","relation":{},"ISSN":["1477-9145","0022-0949"],"issn-type":[{"value":"1477-9145","type":"electronic"},{"value":"0022-0949","type":"print"}],"subject":[],"published":{"date-parts":[[2015,4,1]]}}}