Loss of atm in Zebrafish as a Model of Ataxia-Telangiectasia Syndrome.
Loss of atm in Zebrafish as a Model of Ataxia-Telangiectasia Syndrome.
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DOI：
10.3390/biomedicines10020392
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发表时间：
2022-02-07
期刊：
影响因子：
4.7
通讯作者：
Ye J
中科院分区：
文献类型：
--
作者：
Chen K;Wang P;Chen J;Ying Y;Chen Y;Gilson E;Lu Y;Ye J
共济失调毛细血管扩张突变（ATM）是在人类共济失调毛细血管扩张（a - t）综合征中发生突变的关键DNA损伤信号激酶。这种综合征的特点是神经退行性变、免疫异常、易患癌症和早衰。为了更好地了解ATM在体内的功能，我们设计了一个带有突变ATM基因的活斑马鱼模型。斑马鱼atm功能丧失突变体表现出a - t样运动障碍的特征，包括协调障碍、免疫缺陷和肿瘤发生。atm纯合子鱼的免疫紊乱与造血发育受阻有关，这种情况发生在成年期，导致感染防御能力下降，但对伤口愈合影响不大。在atm突变鱼中发现的恶性肿瘤主要是神经鞘肿瘤和髓系白血病，在A-T患者或atm - / -小鼠中很少发生。这些结果强调了atm在免疫细胞发育过程中的重要性。这种斑马鱼a - t模型为进一步了解a - t肿瘤发生的分子基础和atm在细胞中的作用开辟了一条途径。
Ataxia–telangiectasia mutated (ATM) is a key DNA damage signaling kinase that is mutated in humans with ataxia–telangiectasia (A-T) syndrome. This syndrome is characterized by neurodegeneration, immune abnormality, cancer predisposition, and premature aging. To better understand the function of ATM in vivo, we engineered a viable zebrafish model with a mutated atm gene. Zebrafish atm loss-of-function mutants show characteristic features of A-T-like motor disturbance, including coordination disorders, immunodeficiency, and tumorigenesis. The immunological disorder of atm homozygote fish is linked to the developmental blockade of hematopoiesis, which occurs at the adulthood stage and results in a decrease in infection defense but, with little effect on wound healing. Malignant neoplasms found in atm mutant fish were mainly nerve sheath tumors and myeloid leukemia, which rarely occur in A-T patients or Atm−/− mice. These results underscore the importance of atm during immune cell development. This zebrafish A-T model opens up a pathway to an improved understanding of the molecular basis of tumorigenesis in A-T and the cellular role of atm.
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影响因子：
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作者：
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影响因子：
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通讯作者：
Campisi, Judith
DOI：
10.1073/pnas.1620631114
发表时间：
2017-05-30
影响因子：
11.1
作者：
Botthof, Jan Gregor;Bielczyk-Maczynska, Ewa;Cvejic, Ana
通讯作者：
Cvejic, Ana