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In this study, we investigated the role of Cx37 in fluid homeostasis using mice with a global deletion of Cx37 (Cx37<jats:sup>-\/-<\/jats:sup>mice). Under baseline conditions, Cx37<jats:sup>-\/-<\/jats:sup>had ~40% higher fluid intake associated with ~40% lower urine osmolality compared to wild-type (WT) mice. No differences were observed between genotypes in urinary adenosine triphosphate or prostaglandin E2, paracrine factors that alter renal water handling. After 18-hours of water deprivation, plasma aldosterone and urine osmolality increased significantly in Cx37<jats:sup>-\/-<\/jats:sup>and WT mice; however, the latter remained ~375 mmol\/kg lower in Cx37<jats:sup>-\/-<\/jats:sup>mice, an effect associated with a more pronounced body weight loss despite higher urinary AVP\/creatinine ratios compared to WT mice. Consistent with this, fluid intake in the first 3 hours after water deprivation was 37% greater in Cx37<jats:sup>-\/-<\/jats:sup>vs WT mice. Cx37<jats:sup>-\/-<\/jats:sup>mice showed significantly lower renal AQP2 abundance and AQP2 phosphorylation at serine 256 than WT mice in response to vehicle or dDAVP, suggesting a partial contribution of the kidney to the lower urine osmolality. The abundance and responses of the vasopressin V<jats:sub>2<\/jats:sub>receptor, AQP3, NHE3, NKCC2, NCC, H<jats:sup>+<\/jats:sup>-ATPase, \u03b1ENaC, \u03b3ENaC or Na<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup>-ATPase were not significantly different between genotypes. In summary, these results demonstrate that Cx37 is important for body water handling.<\/jats:p>","DOI":"10.1371\/journal.pone.0244251","type":"journal-article","created":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T20:12:28Z","timestamp":1608235948000},"page":"e0244251","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genetic deletion of connexin 37 causes polyuria and polydipsia"],"prefix":"10.1371","volume":"15","author":[{"given":"Jianxiang","family":"Xue","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linto","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica A.","family":"Dominguez Rieg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A.","family":"Fenton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6082-662X","authenticated-orcid":true,"given":"Timo","family":"Rieg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2020,12,17]]},"reference":[{"key":"pone.0244251.ref001","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1146\/annurev.bi.65.070196.002355","article-title":"Connexins, connexons, and intercellular communication","volume":"65","author":"DA Goodenough","year":"1996","journal-title":"Annu Rev Biochem"},{"issue":"4","key":"pone.0244251.ref002","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1152\/physrev.00007.2003","article-title":"Plasma membrane channels formed by connexins: their regulation and functions","volume":"83","author":"JC S\u00e1ez","year":"2003","journal-title":"Physiological reviews"},{"issue":"5","key":"pone.0244251.ref003","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1515\/BC.2002.076","article-title":"Structural and functional diversity of connexin genes in the mouse and human genome","volume":"383","author":"K Willecke","year":"2002","journal-title":"Biol Chem"},{"issue":"2","key":"pone.0244251.ref004","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.cardiores.2003.11.013","article-title":"Gap junctions and the connexin protein family","volume":"62","author":"G Sohl","year":"2004","journal-title":"Cardiovasc Res"},{"issue":"1","key":"pone.0244251.ref005","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.bbamem.2017.04.024","article-title":"Human diseases associated with connexin mutations","volume":"1860","author":"M Srinivas","year":"2018","journal-title":"Biochim Biophys Acta Biomembr"},{"issue":"5","key":"pone.0244251.ref006","doi-asserted-by":"crossref","first-page":"R1143","DOI":"10.1152\/ajpregu.00808.2009","article-title":"Connexins and the kidney","volume":"298","author":"F Hanner","year":"2010","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"issue":"5","key":"pone.0244251.ref007","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/sj.ki.5002720","article-title":"Function of connexins in the renal circulation","volume":"73","author":"C. 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