Details

Autor(en) / Beteiligte

• Viceconte, Nikenza
• McKenna, Tomás
• Eriksson, Maria
• Ambrósio, Carlos E.

Titel

Low levels of the reverse transactivator fail to induce target transgene expression in vascular smooth muscle cells

Ist Teil von

• PloS one, 2014-08, Vol.9 (8), p.e104098-e104098

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2014

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Hutchinson-Gilford progeria syndrome (HGPS) is a genetic disease with multiple features that are suggestive of premature aging. Most patients with HGPS carry a mutation on one of their copies of the LMNA gene. The LMNA gene encodes the lamin A and lamin C proteins, which are the major proteins of the nuclear lamina. The organs of the cardiovascular system are amongst those that are most severely affected in HGPS, undergoing a progressive depletion of vascular smooth muscle cells, and most children with HGPS die in their early teens from cardio-vascular disease and other complications from atherosclerosis. In this study, we developed a transgenic mouse model based on the tet-ON system to increase the understanding of the molecular mechanisms leading to the most lethal aspect of HGPS. To induce the expression of the most common HGPS mutation, LMNA c.1824C>T; p.G608G, in the vascular smooth muscle cells of the aortic arch and thoracic aorta, we used the previously described reverse tetracycline-controlled transactivator, sm22α-rtTA. However, the expression of the reverse sm22α-transactivator was barely detectable in the arteries, and this low level of expression was not sufficient to induce the expression of the target human lamin A minigene. The results from this study are important because they suggest caution during the use of previously functional transgenic animal models and emphasize the importance of assessing transgene expression over time.