{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T13:57:52Z","timestamp":1787752672588,"version":"build-2784847793"},"reference-count":58,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"DFG-funded Research Training Group"},{"name":"Robert Bosch Stiftung Stuttgart, Germany"},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["SFB 612"],"award-info":[{"award-number":["SFB 612"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["RTGs 1089 and 2816"],"award-info":[{"award-number":["RTGs 1089 and 2816"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["Nu53\/13-1"],"award-info":[{"award-number":["Nu53\/13-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Heterotrimeric Gi proteins are crucial modulators of G protein-coupled receptor signaling, with G\u03b1i2 ubiquitously expressed and implicated in diverse physiological processes. Previous reports described partial lethality in Gnai2-deficient mice, but the timing and mechanism of death remained unclear. Here, we demonstrate that impaired neonatal respiratory adaptation contributes to mortality in Gnai2-deficient neonates. Despite normal Mendelian distribution at birth and no overt malformations, at least 20% of the expected Gnai2-deficient neonates died within minutes after birth, displaying abnormal breathing, cyanosis, and features resembling neonatal respiratory distress syndrome (RDS). Histological and ultrastructural analyses revealed reduced alveolar surface area, thickened septa, increased mesenchymal tissue, and impaired surfactant ultrastructure, despite unaltered alveolar surfactant phospholipid levels. These findings suggest that G\u03b1i2 modulates the structural deployment and functional organization of surfactant within alveoli, although the incomplete phenotype and survival of some neonates indicate a regulatory rather than indispensable role of G\u03b1i2. Our data underscore the complexity of neonatal respiratory adaptation and highlight potential systemic and intercellular mechanisms underlying alveolar stabilization.<\/jats:p>","DOI":"10.3390\/ijms262110655","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:15:14Z","timestamp":1762175714000},"page":"10655","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["G\u03b1i2 Signaling Regulates Neonatal Respiratory Adaptation"],"prefix":"10.3390","volume":"26","author":[{"given":"Veronika","family":"Leiss","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Experimental Therapy and Toxicology, Institute of Experimental and Clinical Pharmacology and Pharmacogenomic, Interfaculty Center for Pharmacogenomics and Drug Research, Eberhard Karls University T\u00fcbingen and University Clinic, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Pexa","sequence":"additional","affiliation":[{"name":"Institute for Biochemistry and Molecular Biology II, Medical Faculty, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Nowacki","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Experimental Therapy and Toxicology, Institute of Experimental and Clinical Pharmacology and Pharmacogenomic, Interfaculty Center for Pharmacogenomics and Drug Research, Eberhard Karls University T\u00fcbingen and University Clinic, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4815-117X","authenticated-orcid":false,"given":"James P.","family":"Bridges","sequence":"additional","affiliation":[{"name":"Department of Medicine, National Jewish Health, Denver, CO 80222, USA"},{"name":"Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2352-2325","authenticated-orcid":false,"given":"Benedikt","family":"Duckworth-Mothes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Experimental Therapy and Toxicology, Institute of Experimental and Clinical Pharmacology and Pharmacogenomic, Interfaculty Center for Pharmacogenomics and Drug Research, Eberhard Karls University T\u00fcbingen and University Clinic, 72076 T\u00fcbingen, Germany"},{"name":"Institute of Clinical Anatomy and Cell Analysis, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Ammon-Treiber","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Clinical Pharmacy, Institute for Pharmacy, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Novakovic","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Experimental Therapy and Toxicology, Institute of Experimental and Clinical Pharmacology and Pharmacogenomic, Interfaculty Center for Pharmacogenomics and Drug Research, Eberhard Karls University T\u00fcbingen and University Clinic, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4692-4575","authenticated-orcid":false,"given":"Franziska","family":"Zeyer","sequence":"additional","affiliation":[{"name":"Interdisciplinary Paediatric Intensive Care Unit 34, Clinic for Paediatrics and Adolescent Medicine, University Clinic T\u00fcbingen, 72016 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartwig","family":"Wolburg","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Neuropathology, Comprehensive Cancer Center, Eberhard Karls University T\u00fcbingen and University Clinic, 72074 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Fallier-Becker","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Neuropathology, Comprehensive Cancer Center, Eberhard Karls University T\u00fcbingen and University Clinic, 72074 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland P.","family":"Piekorz","sequence":"additional","affiliation":[{"name":"Institute for Biochemistry and Molecular Biology II, Medical Faculty, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9984-075X","authenticated-orcid":false,"given":"Matthias","family":"Schwab","sequence":"additional","affiliation":[{"name":"Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, 70376 Stuttgart, Germany"},{"name":"Department of Clinical Pharmacology, Institute of Experimental and Clinical Pharmacology and Pharmacogenomic, Interfaculty Center for Pharmacogenomics and Drug Research, Eberhard Karls University T\u00fcbingen and University Clinic, 72074 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7156-5365","authenticated-orcid":false,"given":"Letizia","family":"Quintanilla-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Neuropathology, Comprehensive Cancer Center, Eberhard Karls University T\u00fcbingen and University Clinic, 72074 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6049-0257","authenticated-orcid":false,"given":"Sandra","family":"Beer-Hammer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Experimental Therapy and Toxicology, Institute of Experimental and Clinical Pharmacology and Pharmacogenomic, Interfaculty Center for Pharmacogenomics and Drug Research, Eberhard Karls University T\u00fcbingen and University Clinic, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5995-6555","authenticated-orcid":false,"given":"Bernd","family":"N\u00fcrnberg","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Experimental Therapy and Toxicology, Institute of Experimental and Clinical Pharmacology and Pharmacogenomic, Interfaculty Center for Pharmacogenomics and Drug Research, Eberhard Karls University T\u00fcbingen and University Clinic, 72076 T\u00fcbingen, Germany"},{"name":"Institute for Biochemistry and Molecular Biology II, Medical Faculty, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"108589","DOI":"10.1016\/j.pharmthera.2024.108589","article-title":"Non-canonical G protein signaling","volume":"255","author":"Reisinger","year":"2024","journal-title":"Pharmacol. 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