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Research Articles
ScienceAsia 33 (2007): 265-271 |doi: 10.2306/scienceasia1513-1874.2007.33.265
ATF3 Transgenic Mice: Structural Analysis of Cardiac Myocytes
Wuthichai Klomkleawa*, Prasarn Tangkawattanab, Tsonwin Haic, Yoshichika Okamotoc, Makoto Mutod and Mamoru Yamaguchie
ABSTRACT: Over-expression of the activating transcription factor 3 (ATF3) in transgenic (TG) mice induces
atrial enlargement. This manuscript reports anatomical and structural alterations in TG mice hearts. A
statistical analysis showed that hearts of the TG mice (0.61±0.2 grams) are significantly heavier than those
of non-transgenic (nTG) mice (0.16±0.03 grams) (P<0.05). The average myocyte cross-sectional area of the
TG mice (172.51±72.72 μm2) was significantly larger than that of nTG mice (74.4±16.46 μm2) (P<0.05).
The alterations varied greatly among individual atria, with and without visible calcification. Approximately
56% of TG mice produced recognizable calcification in the right atrium. Moreover, very few apoptotic cells
were observed. Ultrastructural studies of the enlarged atria showed 1) degeneration and degradation of
cytoplasmic components and mineralization of mitochondria leading to total destruction and death of
myocytes, 2) hyperchromatic-hypertrophic nuclei with various nuclear inclusions, 3) fibrosis and
mineralization of the myocardial layer, and 4) thrombus, cartilage and bone formation. It is possible that
cellular injury would cause energy metabolism impairment and/or sarcolemmal malformation leading to
Ca++ accumulation and subsequent ultrastructural changes. Although pathogenesis of this alteration remains
unclear, ATF3 could be involved in these abnormalities.
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a Department of Veterinary Anatomy, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand.
b Department of Veterinary Anatomy, Faculty of Veterinary Medicine, Khon Kaen University, Khon Kaen, Thailand.
c Department of Molecular and Cellular Biochemistry and Center for Molecular Neurobiology, The Ohio
State University, Columbus, Ohio, USA.
d Department of Veterinary Surgery, School of Veterinary Medicine, Azabu University, Kanagawa, Japan.
e Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University,
Columbus, Ohio, USA.
* Corresponding author, E-mail: Wuthichai.K@Chula.ac.th
Received 15 Feb 2006, Accepted 9 Jan 2007
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