{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:54:14Z","timestamp":1790816054238,"version":"4.1.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"7","license":[{"start":{"date-parts":[[2019,7,1]],"date-time":"2019-07-01T00:00:00Z","timestamp":1561939200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,7]]},"abstract":"\n The melanocortin-2-receptor (MC2R), also known as the ACTH receptor, is a critical component of the hypothalamic\u2013pituitary\u2013adrenal axis. The importance of MC2R in adrenal physiology is exemplified by the condition familial glucocorticoid deficiency (FGD), a potentially fatal disease characterised by isolated cortisol deficiency. MC2R mutations cause ~25% of cases. The discovery of a MC2R accessory protein MRAP, mutations of which account for ~20% of FGD, has provided insight into MC2R trafficking and signalling. MRAP is a single transmembrane domain accessory protein highly expressed in the adrenal gland and essential for MC2R expression and function. Mouse models helped elucidate the action of ACTH. The\n Mc2r-<\/jats:italic>\n knockout (\n Mc2r<\/jats:italic>\n \n \u2212<\/jats:sup>\n <\/jats:italic>\n \n \/<\/jats:sup>\n <\/jats:italic>\n \n \u2212<\/jats:sup>\n <\/jats:italic>\n ) mice was the first mouse model developed to have adrenal insufficiency with deficiencies in glucocorticoid, mineralocorticoid and catecholamines. We recently reported the generation of the\n Mrap<\/jats:italic>\n \n \u2212<\/jats:sup>\n <\/jats:italic>\n \n \/<\/jats:sup>\n <\/jats:italic>\n \n \u2212<\/jats:sup>\n <\/jats:italic>\n mice which better mimics the human FGD phenotype with isolated glucocorticoid deficiency alone. The adrenal glands of adult\n Mrap<\/jats:italic>\n \n \u2212<\/jats:sup>\n <\/jats:italic>\n \n \/<\/jats:sup>\n <\/jats:italic>\n \n \u2212<\/jats:sup>\n <\/jats:italic>\n mice were grossly dysmorphic with a thickened capsule, deranged zonation and deranged WNT4\/beta-catenin and sonic hedgehog (SHH) pathway signalling. Collectively, these mouse models of FGD highlight the importance of ACTH and MRAP in adrenal progenitor cell regulation, cortex maintenance and zonation.\n <\/jats:p>","DOI":"10.1530\/ec-19-0190","type":"journal-article","created":{"date-parts":[[2019,6,11]],"date-time":"2019-06-11T07:13:49Z","timestamp":1560237229000},"page":"R122-R130","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":38,"title":["ACTH signalling and adrenal development: lessons from mouse models"],"prefix":"10.1530","volume":"8","author":[{"given":"Tatiana V","family":"Novoselova","sequence":"first","affiliation":[{"name":"1Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J","family":"King","sequence":"additional","affiliation":[{"name":"1Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Guasti","sequence":"additional","affiliation":[{"name":"1Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise A","family":"Metherell","sequence":"additional","affiliation":[{"name":"1Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian J L","family":"Clark","sequence":"additional","affiliation":[{"name":"1Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li F","family":"Chan","sequence":"additional","affiliation":[{"name":"1Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Endocrine Connections"],"original-title":[],"link":[{"URL":"https:\/\/ec.bioscientifica.com\/view\/journals\/ec\/8\/7\/EC-19-0190.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ec.bioscientifica.com\/downloadpdf\/journals\/ec\/8\/7\/EC-19-0190.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:43:31Z","timestamp":1784555011000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/ec\/article\/8\/7\/R122-R130\/527"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7]]},"references-count":0,"journal-issue":{"issue":"7"},"URL":"https:\/\/doi.org\/10.1530\/ec-19-0190","relation":{},"ISSN":["2049-3614"],"issn-type":[{"value":"2049-3614","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7]]}}}