Publications · JCI Insight 2021 · First author

Nuclear membrane ruptures underlie the vascular pathology in a mouse model of Hutchinson-Gilford progeria syndrome

Linked repetitive nuclear membrane rupture, mechanical stress, DNA damage, and smooth-muscle-cell death in progeria.

The question

Progeria destroys the smooth muscle cells of the arteries, but how?

What we found

• Progerin causes repeated nuclear membrane ruptures, DNA damage and death in cultured smooth muscle cells.
• Lower lamin B1 and mechanical stretch, as in the aorta, made ruptures more frequent.
• Raising lamin B1 reduced ruptures, improved survival and made the stiff progerin nucleus more compliant.
• In progeria mice, lamin B1 falls with age while progerin rises, and nuclear ruptures were found in aortic smooth muscle cells before the cells were lost.

Why it matters

It identifies nuclear membrane rupture as a likely cause of the arterial disease in progeria. The paper was featured on the cover of JCI Insight.

Nuclear membrane ruptures underlie the vascular pathology in a mouse model of Hutchinson-Gilford progeria syndrome. JCI Insight (2021). doi:10.1172/jci.insight.151515