Mouse Model of Hutchinson-Gilford Progeria Syndrome (HGPS) and Vascular Abnormalities (G608G) mutated form of human LNMA) for Therapeutic Development

Children with Hutchinson-Gilford progeria syndrome (HGPS) suffer from acceleration of certain aging symptoms, mainly cardiovascular disease that generally leads to death from myocardial infarction and/or stroke. The cause of HGPS has been discovered to be a de novo point mutation in lamin A (LNMA) gene. NHGRI Scientist have generated a transgenic mouse model of HGPS. This mouse carries a bacterial artificial chromosome (BAC) with a De novo mutation 1824 C to T (G608G) mutated form of human LNMA. The transgenic animals lack external phenotype seen in human progeria but have vascular abnormalities that resemble the human phenotype. Specifically, the mice have progressive vascular smooth muscle cell loss in large arteries and replacement with proteoglycan and collagen, that is, they show progressive vascular calcification. This mouse model can be used to further understand the vascular pathology of progeria and to study potential progeria therapies.