Development of SSLP markers in rat models for diabetes and hypertension.

糖尿病和高血压大鼠模型中 SSLP 标记物的开发。

• 批准号: 07557352
• 负责人: SERIKAWA Tadao
• 金额: $ 1.73万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07557352/
• 关键词: rat; microsatellite marker; SSLP marker; hypertinsion; diabetes; genetic analysis; animal model; gene mapping; 遺伝解析

The rat has been widely used as an experimental animal model for many human diseases. They are particularly useful in the study of multifactorial diseases including hypertension and diabetes. To identify genetic loci involved in the pathogenesis of these types of complex diseases, it is necessary to develop detailed genetic map. Therefore, we developed rat SSLP markers in this study. In addition, we mapped disease-related loci in rat models for diabetes or hypertension.1.Rat SSLP markersWe developed 20 polymorphic DNA markers (13 anonymous DNA fragments and 7 rat genes). In addition, we evaluated the PCR primer sets which were supplied from Research Genetics, and mapped 56 new loci in the rat genetic map. Using mouse SSLP primers, we mapped 20SSLP markers in the rat.2.Genetic analysis of rat models for diabetesGenetic analysis of BB/OK rat (a model for type 1 diabetes) suggested that the third gene for susceptibility of diabetes is located near Olf locus (Chr.18). In the KDP rat, a new model for type 1 diabetes, we mapped a major diabetes-susceptible gene (Iddm/kdp1) on the rat chromosome 11. The mapped region was found to be conserved on mouse choromosome 16 and human choromosome 3.3.Genetic analysis of rat models for hypertensionGenetic analysis of SER indicated that Cryg locus (Chr.9) were cosegragated with high blood pressure. Pkata locus (Chr.8) was cosegregated with decreased blood pressure in SER and DIS/Eis (Dahl rat). In addition, Gja1 locus(Chr 18) cosegeregated with body weight in SHR.

大鼠已被广泛用作许多人类疾病的实验动物模型。它们在包括高血压和糖尿病在内的多因素疾病的研究中特别有用。为了确定参与这些类型的复杂疾病的发病机制的遗传位点，有必要开发详细的遗传图谱。因此，我们在本研究中开发了大鼠SSLP标记物。此外，我们还对糖尿病和高血压大鼠模型的疾病相关位点进行了定位。1.大鼠SSLP标记我们开发了20个多态性DNA标记（13个匿名DNA片段和7个大鼠基因）。此外，我们评估了从Research Genetics提供的PCR引物组，并在大鼠遗传图谱中定位了56个新的基因座。2.糖尿病大鼠模型的遗传学分析对BB/OK大鼠（1型糖尿病模型）的遗传学分析表明，糖尿病易感性的第三个基因位于Olf位点附近（第18条染色体）。在KDP大鼠（一种新的1型糖尿病模型）中，我们在大鼠11号染色体上定位了一个主要的糖尿病易感基因（Iddm/kdp 1）。3.高血压大鼠模型的遗传分析SER基因分析表明，Cryg基因座（第9染色体）与高血压共分离。在SER和DIS/Eis（Dahl大鼠）中，Pkata位点（第8染色体）与血压降低共分离。此外，Gja 1基因（Chr 18）与SHR体重呈正相关。

项目成果

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Toyota, M.：“通过代表性差异分析标记构建的大鼠遗传图谱，适合大规模分型。”

Maihara, T.: "Fifty-six new microsatellite markers in the rat genetic linkage map." Transpl. Proc.27. 1502-1504 (1995)

Maihara, T.：“大鼠遗传连锁图中有 56 个新的微卫星标记。”

Terauchi, Y.: "Pancreatic b-cell-specific targeted disruption of glucokinase gene." J. Biol. Chem.270. 30253-30256 (1995)

Terauchi, Y.：“胰腺 b 细胞特异性靶向破坏葡萄糖激酶基因。”

Katsuya, T.: "Gap junction protein locus on chromosome 18 cosegregates with body weight in the spontaneously hypertensive rat." Hypertens. Res.18. 63-67 (1995)

Katsuya, T.：“18 号染色体上的间隙连接蛋白位点与自发性高血压大鼠的体重共分离。”

Liang, P.: "Chromosomal localization of the rat erythropoietin receptor gene by luorescense in situ hybridization." Jpn. J. Genet.70. 525-531 (1995)

梁，P.：“通过荧光原位杂交对大鼠促红细胞生成素受体基因进行染色体定位。”