Study of the expression profile and function of MAGED2 in the developing mouse kidney

Résumé

MAGED2 (Melanoma Antigen-encoding Gene D2) belongs to the MAGE gene family that arose during the evolution of mammals. MAGE proteins are characterized by the presence of a mage homology domain (MHD) that allows them to interact with E3 ubiquitin ligase and to modulate the ubiquitination , and hence the stability of many proteins. Little is knowm about embryonic kidney. A previous study suggested that MAGED2 is expressed in the Thick Ascending Limb of the Loop of Henle (TAL) and the Distal convoluted tubule (DCT) in the human kidney. Loss-of-function mutations in the human MAGED2 gene are responsible for a rare X-linked form of antenatal Bartter syndrome (BS), which is characterized by a defective salt and water reabsorption probably related to impaired expression and/or activity of renal ion transporters such as NKCC2 and NCC. The defective reabsorption causes severe polyhydramnios (excess amniotic fluid), leading to high perinatal mortality, and resolves spontaneously after birth. The work presented here aimed to investigate the expression profile od MAGED2 in the kidneys of mouse fetuses and newborns by immunostaining experiments of tissue section from wild-type mice or from mice expressing a MAGED2 protein with V5 tag. Despite using different antibodies and protocols, we were unable to localize MAGED2. Another part of the work was the begin to characterize the phenotype of mice deficient in MAGED2 (knock-out). We did not observe any major morphological abnormality or calcium deposit in the renal parenchyma of these animals. However, we observed a dilatation of the abdominal aorta. At the molecular level, we have observed increased levels of the G-alpha-S (Gα_S) protein in the knock-out kidnezs. We have also confirmed that MAGED2 and Gα_S can be co-immunoprecipitated from kidney lysates. Since signaling trhough Gα_S is important for the control of the vascular tone, it may be involved in the aortic dilataiton observed.

la date de réponse	25 août 2023
langue originale	Anglais
L'institution diplômante	Universite de Namur
Superviseur	Olivier De Backer (Promoteur)