Q&A with Dr Li Chan
Research paper: MRAP deficiency impairs adrenal progenitor cell differentiation and gland zonation
What is new about the study?
Familial Glucocorticoid Deficiency is a rare paediatric condition where the body fails to respond to a hormone from the pituitary gland called ACTH. As a result the newborn/child will not make the stress hormone, cortisol, from the adrenal gland. Mutations in a gene called MRAP (melanocortin 2 receptor accessory protein) is one cause of this condition. In the laboratory we have made a mouse model of this rare paediatric disorder by deleting the MRAP gene. The model perfectly recapitulates what we see in patients and is the first mouse model of its type.
How did you carry out the study?
As part of my Academy of Medical Sciences/MRC Clinician Scientist Fellowship, we spent many years generating this unique model. We showed that in order to survive early treatment with steroid replacement therapy is required. Using state of the art molecular biology techniques we were able to dissect some of the reasons why a lack of MRAP results in adrenal disease and inability to generate cortisol.
Why is the study important?
This is the first model of Familial Glucocorticoid Deficiency (FGD) that perfectly models the human condition. Using this model, we have been able to show that there is an impairment of stem cells in the adrenal gland and a disruption in the zones that are formed within the gland. The model shows the importance of MRAP in adrenal development and function and highlights the potential for regulating the stem cell niche in patients with FGD and other conditions that require glucocorticoid treatment.
What are the wider implications?
Our work increases understanding of adrenal gland development and stem cell behaviour. We hope that in the future we will be able to use this model as a basis of developing therapies for patients with FGD. We will also use our model to study the effects of long-term glucocorticoid deficiency in other organs.
Research paper: ‘MRAP deficiency impairs adrenal progenitor cell differentiation and gland zonation’, by Li Chan et al, The FASEB Journal. doi:10.1096/fj.201701274RR