WEKO3
アイテム
Functional analysis of Rim3 mutation that exhibits aberrant epidermal morphogenesis.
https://ir.soken.ac.jp/records/1002
https://ir.soken.ac.jp/records/1002245be848-8490-4476-b577-940daf4392be
| 名前 / ファイル | ライセンス | アクション |
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要旨・審査要旨 / Abstract, Screening Result (205.3 kB)
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本文 (3.6 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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| 公開日 | 2010-02-22 | |||||
| タイトル | ||||||
| タイトル | Functional analysis of Rim3 mutation that exhibits aberrant epidermal morphogenesis. | |||||
| タイトル | ||||||
| タイトル | Functional analysis of Rim3 mutation that exhibits aberrant epidermal morphogenesis. | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_46ec | |||||
| 資源タイプ | thesis | |||||
| 著者名 |
田中, 成和
× 田中, 成和 |
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| フリガナ |
タナカ, シゲカズ
× タナカ, シゲカズ |
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| 著者 |
TANAKA, Shigekazu
× TANAKA, Shigekazu |
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| 学位授与機関 | ||||||
| 学位授与機関名 | 総合研究大学院大学 | |||||
| 学位名 | ||||||
| 学位名 | 博士（理学） | |||||
| 学位記番号 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 総研大甲第808号 | |||||
| 研究科 | ||||||
| 値 | 生命科学研究科 | |||||
| 専攻 | ||||||
| 値 | 18 遺伝学専攻 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2004-09-30 | |||||
| 学位授与年度 | ||||||
| 値 | 2004 | |||||
| 要旨 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Two dominant mouse skin mutants, Recombinant-induced mutation 3 (Rim3) and Rex denuded (Re<SUP>den</SUP>), arose spontaneously in different inbred strains, but exhibit very similar phenotype of hyperkeratosis and alopecia. Both mutants have a genetic alteration in GasderminA-3 (GsdmA-3), which is a member of novel gene family, Gsdm. The Gsdm family commonly share unique leucine-rich C-terminus domain, but the functions of GsdmA-3 and Gsdm family are largely unknown.<br /> In this study, to elucidate the function of GsdmA-3 in the epidermal morphogenesis, I conducted analysis of spatiotemporal expression patterns of GsdmA-3 and the related genes. In addition, I carried out in-depth characterization of the Rim3 phenotype. The results indicated that GsdmA-3 is specifically expressed in differentiated keratinocytes in epidermis after postnatal stage, but not in proliferating epidermal cells. Immunohistochemical analysis of BrdU-labeled epidermis revealed hyperproliferation and misdifferentiation of the upper follicular cells and the epidermis in the Rim3 mutant. All the results suggested that GsdmA-3 is involved in downregulation of cellproliferation and differentiation of the epidermal stem cells.<br />As collaboration with a research group of National Cancer Institute, Tokyo, it was demonstrated that a human homologue GSDMA has a tumor suppressor activity. Mice heterozygous for Trp53 knockout (Trp53<SUP>-</SUP>) allele are known to frequently develop lymphomas, but never develop skin tumors. Although mice heterozygous for the Rim3 mutation alone develop no skin tumors, I examined whether GsdmA-3 is involved in tumor suppression in the Trp53<SUP>-</SUP> genetic background.<br />To do this, I generated mice heterozygous for both of the Rim3 and Trp53<SUP>-</SUP> alleles. As a result, the double heterozygous mice (GsdmA-3<SUP>Rim3</SUP>/+; Trp53<SUP>+</SUP>/+) developed multiple metastatic squamous cell carcinomas (SCC) as early as 7 months of the age. In conjunction with the data that a human homologue GSDMA is a tumor suppressor for gastric cancer in human, this result suggested that GsdmA-3 has a function to prevent tumor development in the mouse skin as well. | |||||
| 所蔵 | ||||||
| 値 | 有 | |||||
| フォーマット | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | application/pdf | |||||
