TP53 Mutant Versus Wild-Type Zebrafish Larvae Under Starvation Stress: Larvae Can Live Up to 17 Days Post-Fertilization Without Food.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2022-04-12 DOI:10.1089/zeb.2022.0003

K. Voskarides, Constantina Koutsofti, Maria Pozova

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引用次数: 6

Abstract

In this study, an experimental protocol has been developed for comparing survival rates of mutant and wild-type zebrafish larvae under extreme starvation. Zebrafish larvae were placed in 96-well plates at fourth day postfertilization (dpf) and larvae were not fed at all from hatching to cease. Zdf1 zebrafish line was used, a strain carrying the (cancer) pathogenic TP53-M214K amino acid substitution. TP53-M214 corresponds to the human TP53-M246 and both residues are located on the DNA-binding domain of the p53 protein. Survival statistical analysis did not show any significant difference in the overall survival rates between homozygous mutant and wild-type larvae. When considering 15 dpf as the endpoint of the experiment (66% of larvae died), a borderline statistical significance was observed for the dominant model of inheritance (p = 0.015; relative hazard = 0.8320). Despite the fact yolk sac of larvae is depleted at 7-8 dpf, 34% of larvae survive until 15 dpf and 1.5% until 17 dpf. Concluding, three main results derive from this study: (1) pathogenic homozygous mutations in TP53 probably do not alter survival rates of zebrafish larvae under starvation; (2) zebrafish larvae can live up to 17 dpf without food, surviving only with their initial nutritional supplies; and (3) an easy and affordable protocol has been developed for estimating survival rates of zebrafish larvae under stressful conditions.

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TP53突变体与野生型斑马鱼在饥饿压力下的幼虫:幼虫在受精后不进食可存活长达17天。

在这项研究中，制定了一项实验方案，用于比较突变型和野生型斑马鱼幼虫在极端饥饿下的存活率。斑马鱼幼虫在受精后第四天（dpf）被放置在96孔板中，从孵化到停止都不喂食。使用Zdf1斑马鱼系，一种携带（癌症）致病性TP53-M214K氨基酸取代的菌株。TP53-M214对应于人TP53-M246，并且两个残基都位于p53蛋白的DNA结合结构域上。存活统计分析没有显示纯合突变体和野生型幼虫之间的总存活率有任何显著差异。当考虑15dpf作为实验的终点（66%的幼虫死亡）时，观察到显性遗传模型的临界统计显著性（p = 0.015；相对危险 = 0.8320）。尽管幼虫的卵黄囊在7-8dpf时耗尽，但34%的幼虫存活到15dpf，1.5%的幼虫存活直到17dpf。最后，本研究得出三个主要结果：（1）TP53的致病性纯合突变可能不会改变斑马鱼幼虫在饥饿条件下的存活率；（2）斑马鱼幼虫在没有食物的情况下可以存活17 dpf，只有靠最初的营养供应才能生存；以及（3）已经开发了一种简单且负担得起的方案来估计斑马鱼幼虫在压力条件下的存活率。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.