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dc.contributor.authorNovoselova, Ten_US
dc.contributor.authorKing, Pen_US
dc.contributor.authorGuasti, Len_US
dc.contributor.authorMetherell, LAen_US
dc.contributor.authorClark, AJLen_US
dc.contributor.authorChan, LFen_US
dc.date.accessioned2019-08-19T14:33:43Z
dc.date.available2019-06-10en_US
dc.date.issued2019-06-01en_US
dc.identifier.issn2049-3614en_US
dc.identifier.urihttps://qmro.qmul.ac.uk/xmlui/handle/123456789/59205
dc.description.abstractThe melanocortin-2-receptor (MC2R), also known as the ACTH receptor, is a critical component of the hypothalamic-pituitary-adrenal 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 Mc2r knockout (Mc2r-/-) 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 Mrap-/- mice which better mimics the human FGD phenotype with isolated glucocorticoid deficiency alone. The adrenal glands of adult Mrap-/- 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.en_US
dc.description.sponsorshipMedical Research Council UK (MRC/Academy of Medical Sciences Clinician Scientist Fellowship Grant G0802796 to L F Chan).en_US
dc.languageengen_US
dc.language.isoenen_US
dc.relation.ispartofEndocr Connecten_US
dc.rightsCreative Commons Attribution 4.0 International License
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleACTH signalling and adrenal development: lessons from mouse models.en_US
dc.typeArticle
dc.rights.holder© 2019 The Authors.
dc.identifier.doi10.1530/EC-19-0190en_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/31189126en_US
pubs.notesNot knownen_US
pubs.publication-statusPublished onlineen_US
dcterms.dateAccepted2019-06-10en_US
rioxxterms.funderDefault funderen_US
rioxxterms.identifier.projectDefault projecten_US


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Creative Commons Attribution 4.0 International License
Except where otherwise noted, this item's license is described as Creative Commons Attribution 4.0 International License