2006 Fiscal Year Final Research Report Summary
Role of Rab38G protein expressed in specifically in the lower respiratory epithelium in the interstitial lung disease
| Project/Area Number |
15590833
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Kanazawa Medical University |
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Principal Investigator |
OSANAI Kazuhiro Kanazawa Medical University, Dept Medicine, Associate Professor (70221158)
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| Project Period (FY) |
2003 – 2006
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| Keywords | Rab38 small GTPase / Interstitial Lung Disease / Lune surfactant / Hermansky-Pudlak syndrome |
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| Research Abstract |
Ruby rats including Fawn-Hooded and Long Evans Cinnamon/Crj (LEC/Crj) are known as animal model of Hermansky-Pudlak syndrome. We extracted genome DNA from tails of these rats, performed DNA sequence, and found a point mutation in the translation initiation codon in the exon 1 of Rab38 gene, resulting in ATG to ATA that indicates no translation of nucleic acids to amino acids. Western blot analysis on the lung tissue lysates from these rats confirmed no existence of Rab38 protein. These rats had ruby-like dark red eyes and cinnamon-like coat hairs, and showed elongation of bleeding time to more than 15 minutes. Thus, these rats have oculocutaneous albinism. The lungs of LEC/Crj showed emphysema-like appearance, and alveolar type II cells were swelled with cytoplasmic lammelar bodies increased in number and in size. Western blot analysis of bronchoalveolar lavage fluid, lamellar body fraction, and total lung homogenate showed that surfactant protein B was increased in the lung tissue but decreased in the alveolar lumen. Isolated alveolar type II cells from LEC/Crj showed decreased basal secretion of [3H]-rabeled surfactant phosphatidylcholine but remarkably increased agonist-induced secretion. These results indicate that Rab38 deficiency in the rat causes oculocutaneous albinism, bleeding diathesis, and lung disease. As these phenotypes correspond to those of human Hermansky-Pudlak syndrome, it is suggested that genetic abnormality of Rab38 may cause the disease in humans.
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