Progressive Vascular Smooth Muscle Cell Defects in a Mouse Model of Hutchinson-Gilford Progeria Syndrome

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 103; no. 9; pp. 3250 - 3255
• Main Authors: Varga, Renee, Eriksson, Maria, Erdos, Michael R., Olive, Michelle, Harten, Ingrid, Kolodgie, Frank, Capell, Brian C., Cheng, Jun, Faddah, Dina, Perkins, Stacie, Avallone, Hedwig, San, Hong, Qu, Xuan, Ganesh, Santhi, Gordon, Leslie B., Virmani, Renu, Wight, Thomas N., Nabel, Elizabeth G., Collins, Francis S.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 28.02.2006; National Acad Sciences
• Subjects: Animals; Aorta; Biological Sciences; Biology; Blood Pressure; Cardiovascular disease; Children & youth; Chromosomes, Artificial, Bacterial - genetics; Disease Models, Animal; Disease Progression; Exons; Genes; Genetic disorders; Genetic mutation; Genetics; Humans; Lamin Type A - metabolism; Lamins; Medicin och hälsovetenskap; Mice; Microscopy, Electron, Transmission; Muscle, Smooth, Vascular - abnormalities; Muscle, Smooth, Vascular - blood supply; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - pathology; Mutation; Myocytes, Smooth Muscle - metabolism; Myocytes, Smooth Muscle - pathology; Myocytes, Smooth Muscle - ultrastructure; Polymerase chain reaction; Progeria; Progeria - genetics; Progeria - metabolism; Progeria - pathology; Progeria - ultrastructure; Rodents; Transgenes - genetics; Transgenic animals
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0600012103

Children with Hutchinson-Gilford progeria syndrome (HGPS) suffer from dramatic acceleration of some symptoms associated with normal aging, most notably cardiovascular disease that eventually leads to death from myocardial infarction and/or stroke usually in their second decade of life. For the vast majority of cases, a de novo point mutation in the lamin A (LMNA) gene is the cause of HGPS. This missense mutation creates a cryptic splice donor site that produces a mutant lamin A protein, termed "progerin," which carries a 50-aa deletion near its C terminus. We have created a mouse model for progeria by generating transgenics carrying a human bacterial artificial chromosome that harbors the common HGPS mutation. These mice develop progressive loss of vascular smooth muscle cells in the medial layer of large arteries, in a pattern very similar to that seen in children with HGPS. This mouse model should prove valuable for testing experimental therapies for this devastating disorder and for exploring cardiovascular disease in general.