dc.contributor.author | Novoselova, TV | en_US |
dc.contributor.author | King, PJ | en_US |
dc.contributor.author | Guasti, L | en_US |
dc.contributor.author | Metherell, LA | en_US |
dc.contributor.author | Clark, AJL | en_US |
dc.contributor.author | Chan, LF | en_US |
dc.date.accessioned | 2019-08-19T14:33:43Z | |
dc.date.available | 2019-06-10 | en_US |
dc.date.issued | 2019-07 | en_US |
dc.identifier.issn | 2049-3614 | en_US |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/59205 | |
dc.description.abstract | The 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.sponsorship | Medical Research Council UK (MRC/Academy of Medical Sciences Clinician Scientist Fellowship Grant G0802796 to L F Chan). | en_US |
dc.format.extent | R122 - R130 | en_US |
dc.language | eng | en_US |
dc.language.iso | en | en_US |
dc.relation.ispartof | Endocr Connect | en_US |
dc.rights | Creative Commons Attribution 4.0 International License | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | ACTH | en_US |
dc.subject | MC2R | en_US |
dc.subject | MRAP | en_US |
dc.subject | adrenal | en_US |
dc.subject | stem cells | en_US |
dc.title | ACTH signalling and adrenal development: lessons from mouse models. | en_US |
dc.type | Article | |
dc.rights.holder | © 2019 The Authors. | |
dc.identifier.doi | 10.1530/EC-19-0190 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/31189126 | en_US |
pubs.issue | 7 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 8 | en_US |
dcterms.dateAccepted | 2019-06-10 | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |