2004 Fiscal Year Final Research Report Summary
Generation of sarcolipin heart-specific transgenic mice and molecular mechanism of atrial chamber-specific expression
| Project/Area Number |
15500288
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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 |
Neurophysiology and muscle physiology
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| Research Institution | Yokohama City University |
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Principal Investigator |
MINAMISAWA Susumu Yokohama City University, School of Medicine, Associate Professor, 医学部, 助教授 (40257332)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIKAWA Yoshihiro Yokohama City University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (40305470)
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| Project Period (FY) |
2003 – 2004
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| Keywords | gene expression / heart function / calcium / transcriptional activity / transgenic mouse / retinoic acid / thyroid hormone |
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| Research Abstract |
I. Cardiac dysfunction sarcolipin heart-specific transgenic mice
In vivo echocardiography and hemodynamic study demonstrated that cardiac function, especially diastolic function was impaired in sarcolipin (SLN) heart-specific transgenic mice when compared with those in age-matched control mice. Although SIN heart-specific transgenic mice did not exhibited either cardiac hypertrophy or dilation, molecular markers of cardiac hypertrophy such as ANF and BNP were up regulated, suggesting masked cardiac remodeling in SLN heart-specific transgenic mine. These data indicate that SLN play an important role in atrial function via regulation of SERCA2a activity.
II. Anaiysisi of mouse sarcolipin promoter and its transcriptional regulation
We cloned a 2.3-kilobase pair DNA fragment encompassing the 5'-flanking region of the mouse SLN gene and examined the effect of retinoic acid on its promoter activity. Transient transfection of H9C2 with F1-luciferase (-2237 to +62 nucleotides) yielded a 40-fold increase in promoter activity. Transient transfection of a series of 5'→3' deletion constructs of F1-luciferase suggested that the minimal region for full activation of the SLN promoter activity is located up to -326 nucleotides and that negative regulatory elements of RA were located between -2237 and -326 nucleotides. The present data indicate that the expression of SLN mRNA is likely regulated by retinoic acid, at least in part, at transcriptional level. In addition, we found that pressure overload, retinoic acid and thyroid hormono down-regulated the expression of SLN mRNAs.
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