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Shortened Life Span, Bradycardia, and Hypotension in Mice with Targeted Expression of an Igf2 Transgene in Smooth Muscle Cells

Departments of Medicine (Experimental Cardiovascular Research) (S.Z., L.P., A.B.T., J.N.) and Experimental Research (C.-M.C., Z.Q.), University of Lund, Malmö General Hospital, 205 02 Malmö, Sweden; and Department of Cell and Molecular Biology (J.T.), Karolinska Institutet, 171 77 Stockholm, Sweden

Address all correspondence and requests for reprints to: Silvio Zaina, Department of Clinical Biochemistry, Sector 3014, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. E-mail: zailund{at}yahoo.com.

IGF2 is known to affect the normal development and pathology of the cardiovascular system. We previously created mutant mice with targeted expression of an Igf2 transgene in the smooth muscle cells and showed that these mice spontaneously develop aortic intimal cushions. In the present work, we provide a general description of the phenotype of two independent lines of heterozygous transgenics. These mice showed organomegaly and a shortened life span. The latter trait was stronger in the line with a relatively more marked organomegaly and more pronounced in males than females in both lines. Postmortem histology revealed gross abnormalities of the cardiac architecture, suggesting that transgenic mice may accumulate lethal cardiovascular defects. Accordingly, apparently normal transgenic mice had mild cardiomegaly, an enlarged left ventricle, bradycardia, and hypotension. These observations are discussed in the light of the proposed therapeutic use of IGF2 in human cardiac diseases.

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