{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:55:19Z","timestamp":1790816119730,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,6,7]],"date-time":"2018-06-07T00:00:00Z","timestamp":1528329600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["UK MR\/K020455\/1"],"award-info":[{"award-number":["UK MR\/K020455\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Melanocortin 2 receptor accessory protein (MRAP) is a single transmembrane domain accessory protein and a critical component of the hypothamo\u2010pituitary\u2010adrenal axis. MRAP is highly expressed in the adrenal gland and is essential for adrenocorticotropin hormone (ACTH) receptor expression and function. Human loss\u2010of\u2010function mutations in\n                    <jats:italic>MRAP<\/jats:italic>\n                    cause familial glucocorticoid (GC) deficiency (FGD) type 2 (FGD2), whereby the adrenal gland fails to respond to ACTH and to produce cortisol. In this study, we generated\n                    <jats:italic>Mrnp<\/jats:italic>\n                    \u2010null mice to study the function of MRAP\n                    <jats:italic>in vivo.<\/jats:italic>\n                    We found that the vast majority of\n                    <jats:italic>\n                      Mrap\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice died at birth but could be rescued by administration of corticosterone to pregnant dams. Surviving\n                    <jats:italic>\n                      Mrap\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice developed isolated GC deficiency with normal min\u2010 eralocorticoid and catecholamine production, recapitulating FGD2. The adrenal glands of adult\n                    <jats:italic>\n                      Mrap\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice were small, with grossly impaired adrenal capsular morphology and cortex zonation. Progenitor cell differentiation was significantly impaired, with dysregulation of WNT4\/\u03b2\u2010catenin and sonic hedgehog pathways. These data dem onstrate the roles of MRAP in both steroidogenesis and the regulation of adrenal cortex zonation. This is the first mouse model of isolated GC deficiency and reveals the role of MRAP in adrenal progenitor cell regulation and cortex zonation.\u2014Novoselova, T. V., Hussain, M., King, P. J., Guasti, L., Metherell, L. A., Charalambous, M., Clark, A. J. L., Chan, L. F. MRAP deficiency impairs adrenal progenitor cell differentiation and gland zonation.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    32, 6186\u20136196 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201701274rr","type":"journal-article","created":{"date-parts":[[2018,6,7]],"date-time":"2018-06-07T17:29:10Z","timestamp":1528392550000},"page":"6186-6196","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["MRAP deficiency impairs adrenal progenitor cell differentiation and gland zonation"],"prefix":"10.1096","volume":"32","author":[{"given":"Tatiana V.","family":"Novoselova","sequence":"first","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine Queen Mary University of London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mashal","family":"Hussain","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine Queen Mary University of London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"King","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine Queen Mary University of London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Guasti","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine Queen Mary University of London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise A.","family":"Metherell","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine Queen Mary University of London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika","family":"Charalambous","sequence":"additional","affiliation":[{"name":"Medical and Molecular Genetics King's College London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian J. 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