| Project/Area Number |
11671077
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Embryonic/Neonatal medicine
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| Research Institution | Kyoto Prefectural University of Medicine (2000)
Tokyo Women's Medical University (1999) |
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Principal Investigator |
YASUI Hiroshi (2000) Kyoto Prefectural University of Medicine, Department of medicine, assistant, 医学部, 助手 (60210241)
森島 正恵 (1999) 東京女子医科大学, 医学部, 助手 (00241068)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAZAWA Makoto Tokyo Women's Medical University of Medicine, Department of medicine, professor, 教授 (10075567)
安井 寛 京都府立医科大学, 医学部, 助手 (60210241)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | retinoic acid / cardiac anomaly / mouse / 内蔵心房錯位 / nodal / lefty |
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| Research Abstract |
Retinoic acid (RA) treatment of pregnant mouse at embryonic day (ED) 6.5 induces right isomerism, anomalous looping and AV cushion dysplasia in about 30% of the embryos, in which unilateral ventricular hypoplasia was often associated. In such embryos, AV orifice to the hypoplastic ventricle was usually stenotic because of malalignment between the interventriclar septum and AV cushion. AV cushion has three lobes in the typical cases, instead of two major and two minor lobes in the normal ones. In the present study, we evaluated the ventricular motion in the RA-treated embryos by in-vivo observation and ventricular area measurement followed by morphological examination. In-vivo observation of the cardiac motion of live embryos enabled us to accurately evaluate the ventricular volume, not influenced by fixation state as in the standard morphological examination, and to correlate it with the ventricular dynamics. The progress of unilateral ventricular hypoplasia was associated with characteristic inflow tract anomaly and inflow disturbance. Furthermore, among cases of category A, one case had only unilateral inflow delay and the other 5 cases had both unilateral ventriclar hypoplasia and inflow delay, suggesting that inflow disturbance is likely to precede the progress of ventriclar hypoplasia. Thus, left ventricular hypoplasia with asplenia syndrome might be caused by inflow restriction to the left venrticle associated with AV cushion dysplasia. Next, we examined the expression of nodal and lefty in the somite stage embryos from dams treated with retinoic acid. Both genes were expressed on left and/or right side and in a sptted and mosaic pattern, in contrast to normal embryos who express the genes on the left side in a continuous pattern. The period of expression was altered and variable. In summary, retinoic acid-induced cardiac anomaly was caused by altered gene expression and intracardiac hemodynamics.
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