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Article

Genetic analysis of genes causing hypertension and stroke in spontaneously hypertensive rats: Gene expression profiles in the kidneys

  • Authors:
    • Yuko Watanabe
    • Momoko Yoshida
    • Kyosuke Yamanishi
    • Hideyuki Yamamoto
    • Daisuke Okuzaki
    • Hiroshi Nojima
    • Teruo Yasunaga
    • Haruki Okamura
    • Hisato Matsunaga
    • Hiromichi Yamanishi
  • View Affiliations / Copyright

    Affiliations: Hirakata General Hospital for Developmental Disorders, Hirakata, Osaka 573-0122, Japan, Department of Neuropsychiatry, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan, DNA-Chip Development Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan, Department of Genome Informatics, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan
  • Pages: 712-724
    |
    Published online on: July 10, 2015
       https://doi.org/10.3892/ijmm.2015.2281
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Abstract

Spontaneously hypertensive rats (SHRs) and stroke-prone SHRs (SHRSP) are frequently used as models not only of essential hypertension and stroke, but also of attention-deficit hyperactivity disorder (ADHD). Normotensive Wistar-Kyoto (WKY) rats are normally used as controls in these studies. In the present study, we aimed to identify the genes causing hypertension and stroke, as well as the genes involved in ADHD using these rats. We previously analyzed gene expression profiles in the adrenal glands and brain. Since the kidneys can directly influence the functions of the cardiovascular, endocrine and sympathetic nervous systems, gene expression profiles in the kidneys of the 3 rat strains were examined using genome-wide microarray technology when the rats were 3 and 6 weeks old, a period in which rats are considered to be in a pre-hypertensive state. Gene expression profiles were compared between the SHRs and WKY rats and also between the SHRSP and SHRs. A total of 232 unique genes showing more than a 4-fold increase or less than a 4-fold decrease in expression were isolated as SHR- and SHRSP-specific genes. Candidate genes were then selected using two different web tools: the 1st tool was the Database for Annotation, Visualization and Integrated Discovery (DAVID), which was used to search for significantly enriched genes and categorized them using Gene Ontology (GO) terms, and the 2nd was Ingenuity Pathway Analysis (IPA), which was used to search for interactions among SHR- and also SHRSP‑specific genes. The analyses of SHR-specific genes using IPA revealed that B-cell CLL/lymphoma 6 (Bcl6) and SRY (sex determining region Y)-box 2 (Sox2) were possible candidate genes responsible for causing hypertension in SHRs. Similar analyses of SHRSP-specific genes revealed that angiotensinogen (Agt), angiotensin II receptor-associated protein (Agtrap) and apolipoprotein H (Apoh) were possible candidate genes responsible for triggering strokes. Since our results revealed that SHRSP-specific genes isolated from the kidneys of rats at 6 weeks of age, included 6 genes related to Huntington's disease, we discussed the genetic association between ADHD and Huntington's disease.
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Spandidos Publications style
Watanabe Y, Yoshida M, Yamanishi K, Yamamoto H, Okuzaki D, Nojima H, Yasunaga T, Okamura H, Matsunaga H, Yamanishi H, Yamanishi H, et al: Genetic analysis of genes causing hypertension and stroke in spontaneously hypertensive rats: Gene expression profiles in the kidneys. Int J Mol Med 36: 712-724, 2015.
APA
Watanabe, Y., Yoshida, M., Yamanishi, K., Yamamoto, H., Okuzaki, D., Nojima, H. ... Yamanishi, H. (2015). Genetic analysis of genes causing hypertension and stroke in spontaneously hypertensive rats: Gene expression profiles in the kidneys. International Journal of Molecular Medicine, 36, 712-724. https://doi.org/10.3892/ijmm.2015.2281
MLA
Watanabe, Y., Yoshida, M., Yamanishi, K., Yamamoto, H., Okuzaki, D., Nojima, H., Yasunaga, T., Okamura, H., Matsunaga, H., Yamanishi, H."Genetic analysis of genes causing hypertension and stroke in spontaneously hypertensive rats: Gene expression profiles in the kidneys". International Journal of Molecular Medicine 36.3 (2015): 712-724.
Chicago
Watanabe, Y., Yoshida, M., Yamanishi, K., Yamamoto, H., Okuzaki, D., Nojima, H., Yasunaga, T., Okamura, H., Matsunaga, H., Yamanishi, H."Genetic analysis of genes causing hypertension and stroke in spontaneously hypertensive rats: Gene expression profiles in the kidneys". International Journal of Molecular Medicine 36, no. 3 (2015): 712-724. https://doi.org/10.3892/ijmm.2015.2281
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Spandidos Publications style
Watanabe Y, Yoshida M, Yamanishi K, Yamamoto H, Okuzaki D, Nojima H, Yasunaga T, Okamura H, Matsunaga H, Yamanishi H, Yamanishi H, et al: Genetic analysis of genes causing hypertension and stroke in spontaneously hypertensive rats: Gene expression profiles in the kidneys. Int J Mol Med 36: 712-724, 2015.
APA
Watanabe, Y., Yoshida, M., Yamanishi, K., Yamamoto, H., Okuzaki, D., Nojima, H. ... Yamanishi, H. (2015). Genetic analysis of genes causing hypertension and stroke in spontaneously hypertensive rats: Gene expression profiles in the kidneys. International Journal of Molecular Medicine, 36, 712-724. https://doi.org/10.3892/ijmm.2015.2281
MLA
Watanabe, Y., Yoshida, M., Yamanishi, K., Yamamoto, H., Okuzaki, D., Nojima, H., Yasunaga, T., Okamura, H., Matsunaga, H., Yamanishi, H."Genetic analysis of genes causing hypertension and stroke in spontaneously hypertensive rats: Gene expression profiles in the kidneys". International Journal of Molecular Medicine 36.3 (2015): 712-724.
Chicago
Watanabe, Y., Yoshida, M., Yamanishi, K., Yamamoto, H., Okuzaki, D., Nojima, H., Yasunaga, T., Okamura, H., Matsunaga, H., Yamanishi, H."Genetic analysis of genes causing hypertension and stroke in spontaneously hypertensive rats: Gene expression profiles in the kidneys". International Journal of Molecular Medicine 36, no. 3 (2015): 712-724. https://doi.org/10.3892/ijmm.2015.2281
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