Mouse models for understanding the molecular mechanism of bone disease in Hutchinson-Gilford progeria syndrome

Abstract: Aging is a complex process affecting all people. Intense research is applied to elucidate the biological basis of aging and disease that develop with aging. Studies of progeroid syndromes, where aging happens in an accelerated speed, might be useful to understand the molecular mechanisms in physiological aging. Hutchinson-Gilford progeria syndrome (HGPS or progeria) is a very rare, fatal genetic disease, with an incidence of 1 in 4-8 million live births, which causes segmental premature aging in children. Affected individuals are born looking healthy, but develop symptoms of disease within their first years of life. Signs of progeria include growth retardation, loss of body fat and hair, skin changes, stiffness of joints, hip dislocations and generalized atherosclerosis and cardiovascular disease. Children with HGPS die of heart disorders or stroke at an average age of 13 years. The aim of this thesis is to increase the understanding of the molecular mechanisms underlying progeria. For this purpose, we developed tissue- specific inducible mouse models for the most common HGPS mutation in the LMNA gene (c.1824C