1991 Fiscal Year Final Research Report Summary
Study on abnormal GH gene expression in spontaneous dwarf rats
| Project/Area Number |
02044118
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Miyazami Medical College |
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Principal Investigator |
KATAKAMI Hideki Miyazaki Medical College, Department of Medicine, 医学部, 助手 (50204417)
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| Co-Investigator(Kenkyū-buntansha) |
OHKUMA Shinnichi Morishita Pharmaceutical Co. Ltd., Research Laboratories, 薬理研究所, 室長代理
MATSUKURA Shigeru Miyazaki Medical College, Department of Medicine, 医学部, 教授 (70030939)
KATO Yukio Gumma University, Institute for Hormone Research, 内分泌研究所・ホルモン測定センタ, 助教授 (30114177)
KEELLY Mayo ノースウェスタン大学, 生化学(アメリカ合衆国), 準教授
MAYO Kelly Northwestern University, Department of Biochemistry, Molecular Biology and Cell
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| Project Period (FY) |
1990 – 1991
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| Keywords | spontaneous dwarf rat / isolated GH deficiency / point mutation of rat GH gene / GH-releasing hormone / somatostatin / hGH / GRF-transgenic rat / hGRF / GH EIA |
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| Research Abstract |
A strain of spontaneous dwarf rats (dr) was recently discovered in Japan. The type of inheritance is an autosomal recessive. The body weight of adult homozygous rats (dr +/+) is from one third to one fourth of that of heterozygotes (dr +/-). Studies utilizing immunocytochemical techniques have so far shown that the strain has an isolated pituitary GH deficiency. Priming of the pituitary GH with human GRF (1-29) NH2 (10 mug, bid, sc x5 d) in female animals failed to stimulate body growth, GH secretion (serum GH levels : ND) or to increase the pituitary GH content (0.06% of control). When hGH (200 mIU, bid, sc x 5d) was given, animals showed increase in body weight (52 g vs. 3g with saline) in male dwarf animals. GRH content in these animals was 45 % of that in controls before treatment. GH treatment partially restored the decreased GRH content (70% of control). The patterns of HPLC analysis of the GRH and SRIF in dr +/+ were identical to those in dr+/-. GRH-containing cells of the hypothalamus in dwarf animals appeared normal in shape and distribution. Nonhem, analysis of total hypothalamic RNA showed an increase in the GRH MRNA of normal size (2-4folds increase of dr+/-). Southem analysis of hepatic DNA (EcoRl or Hind III digest) for GH and PRL appeared normal. In contrast, Nonhem analysis of total pituitary RNA showed an almost total loss of the GH MRNA band of normal size while the PRL MRNA appeared normal. The sequence analysis of both CDNA and genomic DNA of GH in the dr+/+ disclosed two point mutations, one at the junction between 3th intron and the 4th exon, the other within the 5th exon of GH gene. A sensitive HGRF EIA is established for the screening of transgenic dwarf rats which bear metallothinein-coupled HGH/GRF genes.
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Research Products
(12 results)
