Point mutation I634A in the glucocorticoid receptor causes embryonic lethality by reduced ligand binding.

ABSTRACT: The glucocorticoid (GC) receptor (GR) is essential for normal development and in the initiation of inflammation. Healthy GR^dim/dim mice with reduced dimerization propensity due to a point mutation (A465T) at the dimer interface of the GR DNA-binding domain (DBD) (here GR^D/D) have previously helped to define the functions of GR monomers and dimers. Since GR^D/D retains residual dimerization capacity, here we generated the dimer-nullifying double mutant GR^D+L/D+L mice, featuring an additional mutation (I634A) in the ligand-binding domain (LBD) of GR. These mice are perinatally lethal, as are GR^L/L mice (these mice have the I634A mutation but not the A465T mutation), displaying improper lung and skin formation. Using embryonic fibroblasts,

SUBMITTER: Timmermans S 

PROVIDER: S-EPMC8808175 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature