Establishment of hypertansive congenic Strains

高血压同系株的建立

• 批准号: 08670251
• 负责人: NABIKA Toru
• 金额: $ 1.41万
• 依托单位: Shimane Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670251/
• 关键词: essential hypertension; quantitative genetics; spantaneously hypertensive rats; congenic strains; 本能性高血圧; 遺伝子

We have been developing congenic rat strains that possess the hypertension genes of stroke-prone spontaneously hypertensive rats (SHRSP) on the background of a normotensive control, Wistar-Kyoto rats (WKY).1) Preparation of genetic markersa) We selected several genes probably located in the hypertension-related region on rat chromosome 1by comparing rat genome with mouse and human genomes. We isolated 11 genetic markers from the genomic clones of the corresponding rat genes.b) We applied the randomly amplified microsatellite polymorphisms (RAMP) method (Wu et al., 1994) to get more than 100 codominant markers that are polymorphic between SHRSP and WKY.2) Construction of the congenic strainsSHRSP were sequencially backcrossed to WKY for 5 generations to get the semi-congenic strains (more than 95% of genome were from WKY). Genotypes of the backcross rats of each generation were screened by genotyping of microsatellite markers. We have so far obtained 6 semi-congenic strains that have different regions on rat chomosome 1.We now check blood pressure of these strains as well as backcross them further to make complete congenic strains.

我们一直在开发具有卒中易感自发性高血压大鼠(SHRSP)高血压基因的同源大鼠品系，以血压正常的Wistar-京都大鼠(WKY)为背景。1)遗传标记的制备)通过比较大鼠基因组与小鼠和人的基因组，我们选择了几个可能位于大鼠1号染色体高血压相关区域的基因。我们从相应的大鼠基因组克隆中分离出11个遗传标记。b)应用随机扩增微卫星多态(RAMP)方法(Wu等，1994)获得了100多个在SHRSP和WKY之间具有多态性的共显性标记。2)构建SHRSP同源品系，将SHRSP连续回交到WKY上5代，得到半同源品系(95%以上的基因组来自WKY)。利用微卫星标记进行基因分型，筛选各世代回交大鼠的基因分型。到目前为止，我们已经获得了6个在大鼠软骨小体1上具有不同区域的半同源菌株，现在我们检测这些菌株的血压，并将它们进一步回交，形成完整的同源菌株。

项目成果

並河 徹: "特集「小児疾患研究におけるモデル動物」本態性高血圧症(SHR)." 小児外科. 29. 312-318 (1997)

Toru Namikawa：“专题‘儿科疾病研究中的模型动物’原发性高血压 (SHR)。”小儿外科。29. 312-318 (1997)

Notsu Y,Nabika T,Masuda J,Kobayashi S: "Apo (a) phenotype as a risk factor for the silent brain infarction." Jpn.J.Clin.Pathol.45. 122-126 (1997)

Notsu Y、Nabika T、Masuda J、Kobayashi S：“Apo (a) 表型是无症状脑梗塞的危险因素。”

Ishinaga Y,Nabika T,Hiraoka J,Shimada T,Nara Y,Yamori Y: "Re-evaluation of the SA gene in the kidneys of the spontaneously hypertensive and Wistar-Kyoto rats." Clin.Exp.Pharm.Phys.24. 18-22 (1997)

Ishinaga Y、Nabika T、Hiraoka J、Shimada T、Nara Y、Yamori Y：“自发性高血压大鼠和 Wistar-Kyoto 大鼠肾脏中 SA 基因的重新评估。”

Nabika T, Tamiyo Ito, Kazuhiro Kitada, Tadao Serikawa, Tomoji Mashimo, Florent Soubrier, Cecile Julier, et al.: "Comparative mapping of novel simple sequence repeat markers in hypertension-related region on rat chromosome." Mamm.Genome. 8. 215-217 (1997)

Nabika T、Tamiyo Ito、Kazuhiro Kitada、Tadao Serikawa、Tomoji Mashimo、Florent Soubrier、Cecile Julier 等人：“大鼠染色体上高血压相关区域新型简单序列重复标记的比较作图。”

Nabika T: "The spontaneously Hypertensive rat : A genetic model for essential hypertension." Jpn.J.Pediatr.Surg.29. 312-318 (1997)

Nabika T：“自发性高血压大鼠：原发性高血压的遗传模型。”