Shortened life span, bradycardia, and hypotension in mice with targeted expression of an Igf2 transgene in smooth muscle cells.
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.
Department of Medicine (Experimental Cardiovascular Research), University of Lund, Malmö General Hospital, 205 02 Malmö, Sweden. zailund@yahoo.com
Silvio
S
Zaina
Linda
L
Pettersson
Anne Bloch
AB
Thomsen
Chun-Ming
CM
Chai
Zhongquan
Z
Qi
Johan
J
Thyberg
Jan
J
Nilsson
D000818:Animals; D001011:Aorta / Q000473:pathology; D001794:Blood Pressure; D001824:Body Constitution; D001919:Bradycardia / Q000401:mortality / Q000473:pathology / Q000503:physiopathology*; D004562:Electrocardiography; D005260:Female; D015870:Gene Expression / Q000502:physiology; D006330:Heart Defects, Congenital / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D006579:Heterozygote; D007022:Hypotension / Q000401:mortality / Q000473:pathology / Q000503:physiopathology*; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008136:Longevity / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D032389:Myocytes, Smooth Muscle / Q000473:pathology / Q000502:physiology*; D010641:Phenotype; D017678:Sex Distribution; D015996:Survival Rate; D019076:Transgenes / Q000502:physiology
D007335:Insulin-Like Growth Factor II