Klotho 是一個由1014個胺基酸組成的第一型的穿膜蛋白 (Type-I membrane protein) 在人類基因組中的編碼為KL，Klotho基因會轉譯出一種單通道的穿膜蛋白，此種穿膜蛋白會與許多 Fibroblast growth factor 結合並作為其 co-receptor 輔助與其相應之受體結合，Klotho 與衰老 (aging) 也有相當程度的關聯性，Klotho 突變的小鼠相較於野生型小鼠壽命是相對較短的，大約只有野生型小鼠壽命的 5% 左右，並且有提早出現類似人類衰老相似的徵狀或疾病，例如貧血 (anemia)、動脈硬化 (arteriosclerosis)、骨質酥鬆 (osteoporosis)、皮膚老化……等等，但是目前在各個物種上針對 Klotho 在早期發育的方面研究資訊並不充足，目前僅能得知 Klotho 缺陷的老鼠在早期未發現任何 phenotypes，不過我們推測也許是因為小鼠為哺乳類動物，胚胎早期發育在子宮內不易觀察、亦或是帶嚴重缺陷的無法發育而直接成死胎流產，且斑馬魚在 Klotho 方面的研究目前也僅止於發育晚期，故想藉助斑馬魚早期胚胎發育易於觀察之特性，來研究 Klotho 是否會影響早期胚胎發育，根據實驗的結果顯示， knockdown klotho tv-1 後會發生 cell migration 異常的情形以及 knockdown klotho tv-2 會導致細胞分裂異常，故斑馬魚 klotho 對於胚胎發育方面有一定的重要性。

Klotho is an aging-related protein, but little is known about the molecular mechanisms by which Klotho controls early embryonic development. In this study, we aim to investigate the possible molecular mechanisms by a morpholino knockdown approach in a zebrafish model. Our data showed that zebrafish possess two different Klotho spliced forms, which can translate to different polypeptides (klotho tv1：990 a.a; klotho tv2：937 a.a). Knockdown of klotho tv1 resulted in abnormal cell migration during the embryonic developmental process. However, klotho tv2 knowndown embryos were unable to undergo cell cleavage. At the molecular level, whole mount in situ hybridization showed that the expressions of bmp4, gsc, flh and eve1 genes were affected by Klotho. These results suggested that klotho tv1 and klotho tv2 might play different physiological roles during zebrafish embryogenesis.

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材料方法-09
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參考文獻-38
附錄-----41

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