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Rag-dependent and Rag-independent mechanisms of Notch1 rearrangement in thymic lymphomas of Atm-/- and scid mice
https://repo.qst.go.jp/records/45418
https://repo.qst.go.jp/records/45418086eb934-c160-426e-be05-7b1c466b331f
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2009-02-06 | |||||
| タイトル | ||||||
| タイトル | Rag-dependent and Rag-independent mechanisms of Notch1 rearrangement in thymic lymphomas of Atm-/- and scid mice | |||||
| 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_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Tsuji, Hideo
× Tsuji, Hideo× Ishii-Ohba, Hiroko× Noda, Yuko× Kubo, Eiko× Furuse, Takeshi× Tatsumi, Kouichi× 辻 秀雄× 石井 洋子× 野田 攸子× 久保 ゑい子× 古瀬 健× 巽 紘一 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | The pathways of thymic lymphomagenesis are classified as Rag-dependent or -independent according to their dependence on recombination-activating gene (Rag1/2) proteins. The role of the two-lymphoma pathways in oncogene rearrangements and the connection between lymphoma pathways and rearrangement mechanisms, however, remain obscure. We compared the incidence and latency of thymic lymphomas, and associated rearrangements of the representative oncogene Notch1 among Rag2-/-, ataxia telangiectasia mutated (Atm)-/-, and severe combined immune deficiency (scid) mice combined with Rag2 deficiency. Contrary to expectations, Rag2-/- mice were prone to thymic lymphoma development, suggesting the existence of a Rag2-independent lymphoma pathway in Rag2-/- mice. The lymphoma incidence in Rag2-/-Atm-/- mice was lower than that in Atm-/- mice, but higher than that in Rag2-/- mice, indicating that Atm-/- mice develop lymphomas through both pathways. Scid mice developed lymphomas with an incidence and latency similar to Rag2-/-scid mice, suggesting that Rag2-mediated V(D)J recombination-driven events are not necessarily required for lymphomagenesis in scid mice. Notch1 rearrangement mechanisms were classified as Rag2-dependent or Rag2-independent based on the presence of recombination signal-like sequences at rearranged sites. In Rag2-/- lymphomas, Notch1 must be rearranged independently of Rag2 function, implying that Rag2-/- mice are susceptible to lymphomagenesis due to the presence of other rearrangement mechanisms. The results in Atm-/- mice suggest that Notch1 was rearranged through both lymphoma pathways. In scid mice, the frequency of Rag2-mediated rearrangements was relatively low compaired with that in wild-type mice, suggesting that the Rag2-independent lymphoma pathway prevails in the development of thymic lymphoma in scid mice. Thus, two rearrangement mechanisms underlie the lymphoma pathways and constitute the mechanistic bases for lymphomagenesis, thereby providing the molecular criteria for distinguishing between Rag2-dependent and Rag2-independent lymphoma pathways. | |||||
| 書誌情報 |
Fundamental and Molecular Mechanisms of Mutagenesis : A Section of Mutation Research 巻 660, 号 1/2, p. 22-32, 発行日 2009-01 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0027-5107 | |||||
