{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:02:48Z","timestamp":1791118968448,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2008,5,1]],"date-time":"2008-05-01T00:00:00Z","timestamp":1209600000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2008,5]]},"abstract":"<jats:p>Medullary serotonergic (5\u2010HT) neurons are implicated in central chemoreception and 5\u2010HT abnormalities are present in many cases of the sudden infant death syndrome (SIDS). Mice with a targeted disruption of the serotonin transporter (5\u2010HTT) develop in the presence of excess 5\u2010HT in brain extracellular fluid (ECF). As adults they exhibit reduced 5\u2010HT neuron activity and 5\u2010HT<jats:sub>1A<\/jats:sub>receptor binding with varying changes in postsynaptic 5\u2010HT receptor function. They exhibit behavioural phenotypes (anxiety, reduced aggression) but little is known about their control of breathing. We show that conscious adult male and female 5\u2010HTT knockout mice breathing air at room temperature have a higher resting<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/TJP_2871_mu1.gif\" xlink:title=\"inline image\"\/>, breathing frequency and<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/TJP_2871_mu2.gif\" xlink:title=\"inline image\"\/>but a normal body temperature and<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/TJP_2871_mu3.gif\" xlink:title=\"inline image\"\/>ratio (the ventilatory equivalent) compared to wild\u2010type (WT) controls. In hypercapnia, there is a reduced ventilatory response (expressed as the<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/TJP_2871_mu4.gif\" xlink:title=\"inline image\"\/>ratio) that is much more prominent in males (\u221268%) than females (\u221222%). In hypoxia, both males and females exhibit a higher<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/TJP_2871_mu5.gif\" xlink:title=\"inline image\"\/>,<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/TJP_2871_mu6.gif\" xlink:title=\"inline image\"\/>and body temperature but their<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/TJP_2871_mu7.gif\" xlink:title=\"inline image\"\/>ratio is normal. We conclude that 5\u2010HTT knockout mice have a diminished function of the medullary 5\u2010HT system, which is manifest most remarkably in a substantial loss of CO<jats:sub>2<\/jats:sub>sensitivity predominantly in males. This finding supports the importance of medullary 5\u2010HT neurons in central chemoreception. Females either rely less on 5\u2010HT neurons in chemoreception or adapt more readily to the loss of 5\u2010HT function. This genetic model allows examination of the role of excess 5\u2010HT in ECF in the development of the control of breathing and central chemoreception, which may be pertinent to SIDS.<\/jats:p>","DOI":"10.1113\/jphysiol.2008.152231","type":"journal-article","created":{"date-parts":[[2008,3,21]],"date-time":"2008-03-21T00:49:17Z","timestamp":1206060557000},"page":"2321-2329","source":"Crossref","is-referenced-by-count":77,"title":["Serotonin transporter knockout mice have a reduced ventilatory response to hypercapnia (predominantly in males) but not to hypoxia"],"prefix":"10.1113","volume":"586","author":[{"given":"Aihua","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Nattie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,5]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2006.02.012"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1569-9048(02)00038-1"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2003.02960.x"},{"key":"e_1_2_5_5_1","unstructured":"Centers for Disease Control and Prevention(2008).National Center for Health Statistics. CDC WONDER On\u2010line Database compiled from Compressed Mortality File 1999\u20132005 Series 20. No. 2K. 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