Establishment of a strain of the rat with spontaneously occurring hypertrophic cardiomyopathy

自发性肥厚型心肌病大鼠品系的建立

• 批准号: 62580034
• 负责人: KURIBAYASHI Toshiro
• 金额: $ 1.15万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62580034/
• 关键词: WKY; NCrj rats; Hypertrophic cardiomyopathy; 選択交配; 常染色体優性遺伝; 胎仔動脈; 管低形成; 異常心の生前診断

We have reported that myocardial abnormalities quite similar to those of human hypertrophic cardiomyopathy occurs spontaneously in some the rat of WKY/NCrj strain; the rat showed, in the absence of blood pressure elevation, marked cardiac hypertrophy, i.e., greater heart weight and a disproportionately thicker ventricular septum in relation to left ventricular free wall than did rats with normal hearts; furthermore, these rats with a marked cardiac hypertrophy had a marked abnormal arrangement of cardiac muscle fibers and myofibrils, a narrowing of the left ventricular cavity, myocardial fibrosis, and mural arteries with an abnormal wall thickening (Jpn Circ J 51: 573-588, 1987).The purpose of the present project is to establish a strain of rats with a higher incidence of marked cardiac hypertrophy, which shoud be a useful animal model for the study of the human disease. Electrocardiographic recordings revealed that a high QRS complex, an axis deviation of the QRS, and a high T wave are characteristic of the with a marked cardiac hypertrophy. On the basis of these findings, selective breeding of rats with a marked cardiac hypertophy and of rats with a normal heart as the control is now being continued. However, the establishment of these strains may require a long process of selection, since there is an evidence that the underlying gene abnormality has already spread widely in this strain; i.e., the WKY/NCrj strain is an established inbred one persisting for more than 30 generations and quite identical abnormalities of the heart occur in the strain of rats from which the WKY/NCrj diverged.

我们报道，一些WKY/NCrj品系大鼠自发出现与人类肥厚型心肌病非常相似的心肌异常；在没有血压升高的情况下，大鼠表现出明显的心脏肥大，即与正常心脏的大鼠相比，心脏重量更大，心室间隔相对于左心室游离壁不成比例地更厚；此外，这些具有明显心脏肥大的大鼠具有明显的心肌纤维和肌原纤维排列异常、左心室腔变窄、心肌纤维化以及壁动脉壁异常增厚（Jpn Circ J 51：573-588， 1987）。本项目的目的是建立一种具有较高的明显心脏肥大发生率的大鼠品系，这应该是一个有用的动物模型。人类疾病的研究。心电图记录显示高 QRS 波群、QRS 轴偏差和高 T 波是明显心脏肥大的特征。基于这些发现，目前正在继续选择性繁殖具有明显心脏肥大的大鼠和具有正常心脏的大鼠作为对照。然而，这些菌株的建立可能需要一个漫长的选择过程，因为有证据表明潜在的基因异常已经在该菌株中广泛传播；也就是说，WKY/NCrj 品系是一种已确定的近交品系，持续了 30 代以上，并且在 WKY/NCrj 分化的大鼠品系中出现了完全相同的心脏异常。

项目成果

Toshiro,Kuribayashi: Japanese Circulation Journal. 52. 1156-1170 (1988)

栗林敏郎：日本流通杂志。