Progressive vascular smooth muscle cell defects in a mouse model of Hutchinson–Gilford progeria syndrome

Proceedings of the National Academy of Sciences of the United States of America - Tập 103 Số 9 - Trang 3250-3255 - 2006
Renée Varga1, Maria Eriksson2, Michael R. Erdos1, Michelle Olive1, Ingrid A. Harten3,4, Frank D. Kolodgie5, Brian C. Capell1, Jun Cheng6, Dina A. Faddah1, Stacie Perkins1, Hedwig Avallone5, Hong San1, Xuan Qu1, Santhi K. Ganesh1, Leslie B. Gordon7,8, Renu Virmani5, Thomas N. Wight3,4, Elizabeth G. Nabel9,10, Francis S. Collins1
1*Genome Technology Branch and
2Department of Medical Nutrition, Karolinska Institutet, Novum, Halsovagen 7, Hiss E, Plan 6, 141 57 Huddinge, Sweden;
3Department of Pathology, University of Washington, School of Medicine, Seattle, WA 98195
4Department of Pathology, University of Washington School of Medicine, Seattle, WA 98195;; Hope Heart Program, Benaroya Research Institute at Virginia Mason, Seattle, WA 98101-2795;
5CVPath, Inc., 19 Firstfield Road, Gaithersburg, MD 20878;
6Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, 50 South Drive, Bethesda, MD 20892;
7**Department of Pediatrics, Brown Medical School, Providence, RI 02912; and
8**Department of Pediatrics, Brown Medical School, Providence, RI 02912; and; *Genome Technology Branch and
9*Genome Technology Branch and; National Heart, Lung, and Blood Institute, National Institutes of Health, 31 Center Drive, Bethesda, MD 20892
10National Heart, Lung, and Blood Institute, National Institutes of Health, 31 Center Drive, Bethesda, MD 20892

Tóm tắt

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, ade novopoint 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.

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Tài liệu tham khảo

10.1016/S0022-3476(72)80229-4

P. B. Baker, N. Baba, C. P. Boesel Arch. Pathol. Lab. Med 105, 384–386 (1981).

10.1016/S1054-8807(98)00023-4

10.1016/S1054-8807(01)00069-2

10.1080/pdp.21.1.1.13

10.1038/nature01629

10.1126/science.1084125

10.1016/S0140-6736(03)14761-7

10.1136/jmg.2003.015651

10.1136/jmg.2003.014688

10.1136/jmg.2004.019661

S. Huang, B. K. Kennedy, J. Oshima Novartis Found. Symp 264, 197–202, discussion 202-207, 227–230. (2005).

10.1038/nrm1550

10.1101/gad.960502

10.1073/pnas.0506001102

10.1093/hmg/ddg213

10.1083/jcb.147.5.913

10.1038/nature01631

10.1073/pnas.0504641102

10.1006/geno.2000.6451

10.1096/fj.99-0927com

10.1172/JCI200419670

10.1093/hmg/ddi326

10.1194/jlr.R500011-JLR200

10.1073/pnas.0505767102

10.1073/pnas.132252399

10.1101/gr.749203

10.1179/his.1996.19.4.325

10.1161/01.CIR.0000019071.72887.BD

S. L. Lara, S. P. Evanko, T. N. Wight Methods Mol. Biol 171, 271–290 (2001).

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Proceedings of the National Academy of Sciences of the United States of America

Tập 103 Số 9

3250-3255

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