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  1. 020 学位論文
  2. 生命科学研究科
  3. 18 遺伝学専攻

Functional analysis of Rim3 mutation that exhibits aberrant epidermal morphogenesis.

https://ir.soken.ac.jp/records/1002
https://ir.soken.ac.jp/records/1002
245be848-8490-4476-b577-940daf4392be
名前 / ファイル ライセンス アクション
甲808_要旨.pdf 要旨・審査要旨 / Abstract, Screening Result (205.3 kB)
甲808_本文.pdf 本文 (3.6 MB)
Item type 学位論文 / Thesis or Dissertation(1)
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
言語 en
タイトル Functional analysis of Rim3 mutation that exhibits aberrant epidermal morphogenesis.
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

WEKO 10140

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

WEKO 10141

タナカ, シゲカズ

Search repository
著者 TANAKA, Shigekazu

× TANAKA, Shigekazu

WEKO 10142

en TANAKA, Shigekazu

Search repository
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
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
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