人類WWOX基因可轉譯出具有抑制腫瘤生成作用的含雙色胺酸功能區氧化還原酶 (WW domain-containing oxidoreductase, WWOX)，在小鼠又稱為 WOX1 蛋白質。為了研究 WWOX/WOX1 蛋白質在體內的功能，我們實驗室成功地生產出 Wwox-/- 小鼠，而且發現 Wwox-/- 小鼠在出生後一個月內會死亡，顯示 WWOX/WOX1 蛋白質除了具有腫瘤抑制功能外，尚有其他的生理功能。為了研究 WWOX/WOX1 蛋白質在體內的功能，我們利用 Wwox+/+ 與 Wwox+/- 小鼠，建立發炎的實驗動物模式進行研究。我們發現在實驗動物模式中，Wwox+/- 小鼠出現體重急遽下降與死亡的現象。與 Wwox+/+ 小鼠相比之下，Wwox+/- 小鼠脾臟有腫大的情形。此外，在給予處理後的小鼠血清中，也偵測到大量的介白素-6分泌。在實驗動物模式中，小鼠的調控型 T 細胞數量並沒有任何變化，顯示 WWOX/WOX1 蛋白質表現多寡並不影響調控型 T 細胞分化的數量。總結目前的結果，我們推測在小鼠的發炎反應中， WWOX/WOX1 蛋白質扮演重要的調控性角色。

Human WWOX gene encodes a candidate tumor suppressor WW domain-containing oxidoreductase (designed WWOX or murine WOX1). For analyzing the functional roles of WWOX/WOX1 in vivo, we have successfully generated Wwox gene knockout mice in our laboratory. All the whole-body Wwox-/- mice died within a month after birth, suggesting that WWOX/WOX1 functions beyond a tumor suppressor. To investigate the in vivo function of WWOX/WOX1, we tested inflammatory mouse model using Wwox+/+ and Wwox+/- mice. We found that Wwox+/- mice exhibited more severe disease symptoms and higher mortality rate than the wild-type control mice. Compared with Wwox+/+ mice, increased spleen weights were observed in Wwox+/- mice after treatment. High serum levels of interleukin (IL)-6 were detected in treated mice, suggesting that these mice developed more severe inflammatory responses. Comparable numbers of regulatory T cells (Treg) were determined in mice, indicating that WWOX/WOX1 may not affect Treg cell differentiation. Together, our results suggest that WWOX/WOX1 plays important roles in regulating inflammatory responses in mice.

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