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首页> 外文期刊>Endocrinology >Knockdown of type 3 iodothyronine deiodinase severely perturbs both embryonic and early larval development in zebrafish
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Knockdown of type 3 iodothyronine deiodinase severely perturbs both embryonic and early larval development in zebrafish

机译：击倒3型碘甲状腺素去碘酶会严重干扰斑马鱼的胚胎发育和幼虫早期发育

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Exposure to appropriate levels of thyroid hormones (THs) at the right time is of key importance for normal development in all vertebrates. Type 3 iodothyronine deiodinase (D3) is the prime TH-inactivating enzyme, and its expression is highest in the early stages of vertebrate development, implying that it may be necessary to shield developing tissues from overexposure to THs. We used antisense morpholino knockdown to examine the role of D3 during early development in zebrafish. Zebrafish possess 2 D3 genes, dio3a and dio3b. Here, we show that both genes are expressed during development and both contribute to in vivo D3 activity. However, dio3b mRNA levels inembryosare higher, and the effects of dio3b knockdownonD3activityandonthe resulting phenotype are more severe. D3 knockdown induced an overall delay in development, as determined by measurements of otic vesicle length, eye and ear size, and body length. The time of hatching was also severely delayed in D3-knockdown embryos. Importantly, we also observed a severe disturbance of several aspects of development. Swim bladder development and inflation was aberrant as was the development of liver and intestine. Furthermore, D3-knockdown larvae spent significantly less time moving, and both embryos and larvae exhibited perturbed escape responses, suggesting that D3 knockdown affects muscle development and/or functioning. These data indicate that D3 is essential for normal zebrafish embryonic and early larval development and show the value of morpholino knockdown in this model to further elucidate the specific role of D3 in some aspects of vertebrate development.
机译：在正确的时间暴露于适当水平的甲状腺激素（THs）对于所有脊椎动物的正常发育至关重要。 3型碘甲状腺素脱碘酶（D3）是TH的主要失活酶，在脊椎动物发育的早期阶段其表达最高，这意味着可能有必要保护发育中的组织免于THs的过度暴露。我们使用反义吗啉代敲低来检查D3在斑马鱼早期发育过程中的作用。斑马鱼拥有2个D3基因dio3a和dio3b。在这里，我们显示这两个基因在发育过程中均表达，并且都对体内D3活性有贡献。但是，胚胎中的dio3b mRNA水平更高，并且dio3b敲低对D3活性和对产生的表型的影响更为严重。 D3击倒诱导发育的总体延迟，这是通过测量耳泡长度，眼睛和耳朵的大小以及体长确定的。在D3基因敲除的胚胎中，孵化时间也被严重延迟。重要的是，我们还观察到了发展的几个方面的严重干扰。游泳膀胱的发育和膨胀异常，肝和肠的发育也异常。此外，击倒D3的幼虫花费的时间明显更少，并且胚胎和幼虫均表现出扰乱的逃避反应，表明D3击倒会影响肌肉的发育和/或功能。这些数据表明D3对于正常的斑马鱼胚胎和幼虫早期发育必不可少，并显示了吗啉代敲除在该模型中的价值，以进一步阐明D3在脊椎动物发育的某些方面的特定作用。

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