Modeling Principle

This progeria mouse model is based on a point mutation in the Lamin A gene that activates a cryptic splice site in exon 11 (G608G: GGC→GGT). This leads to the deletion of 50 amino acids from the C-terminus of the prelamin A polypeptide. The resulting truncated protein is known as progerin. Progerin retains the CXXF motif but lacks the ZMPSTE24 cleavage site, preventing the normal post-translational processing at the C-terminus. The exposed farnesylated cysteine methyl ester remains permanently attached. Over time, the accumulation of progerin causes various cellular defects and dysfunctions, ultimately leading to aging of cells and tissues.