|Budget Amount *help
¥12,200,000 (Direct Cost : ¥12,200,000)
Fiscal Year 1999 : ¥4,900,000 (Direct Cost : ¥4,900,000)
Fiscal Year 1998 : ¥7,300,000 (Direct Cost : ¥7,300,000)
1) In vivo expression of angiotensinogen gene (AGT) is different between T allele and M allele. We have previously demonstrated about 20% higher expression in T allele than in M allele by way of in vitro experiments. In this study, we have tried to show allele dependent higher expression of AGT in vivo. For this purpose, we collected human cardiac tissue obtained in the operation of coronary artery bypass grafting (CABG). Out of 64 samples, 11 samples were revealed from the patient whose genotype is heterozygous of M235T (MT type). With these 11 samples, we have performed allele specific expression assay with primer pairs of P^<32> end-labeled common and allele specific oligonucleotide primer and Taq DNA ligase. Densitometrically, we found AGT expression from T alleles were 0 to 20% higher than that from M allele. This result may indicate the higher expression of AGT could be the cause of hypertension susceptibility.
2) We tried to show the difference of salt sensitivity in mice whose number of AGT gene copies ranged from 1 to 4. As the developer of these mice claimed, we have observed copy number dependent increase of blood pressure. However, we could not detect significant difference of blood pressure between high salt load (8%) and low salt diet (0.6%) in any combination of mice. Two possibilities could be considered for our result. One could be due to tail-cuff method we employed to measure blood pressure. The other could be due to the mouse strain which may be salt insensitive.