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Time for rethinking the different β‐actin transgenic mouse models?
Cytoskeleton ( IF 2.9 ) Pub Date : 2020-11-29 , DOI: 10.1002/cm.21647
Bieke Vanslembrouck 1 , Christophe Ampe 2 , Jolanda van Hengel 1
Affiliation  

The actin family is crucial for many cellular processes and in mammals muscle and non‐muscle forms exist. The latter group contains cytoplasmic‐β‐actin and cytoplasmic‐γ‐actin, almost identical in amino acid sequence and with a significant functional overlap. We introduce the properties of the Actb gene and mRNA transcript(s) with main focus on the 3′UTR and its unique features, that is, the zipcode and two polyadenylation sites creating transcripts of different lengths. Several transgenic mouse models with a modified Actb locus have been created. The different mouse models can be divided into three groups; that is, 5′ or 3′ insertion models, mouse models with loxP sequences around exon 2–3 resulting in deletion the start codon, and models with gene edited Actb sequences that produces γ‐actin protein instead of β‐actin. Whole body knockouts and, with one exception, insertion models lead to embryonic lethality indicating that the Actb gene or transcripts or translated β‐actin are essential. Tissue specific ablation at later developmental stages lead to no, or mild phenotypes, suggesting that the Actb gene or β‐actin protein is somewhat dispensable. Gene edited Actb mice that produce γ‐actin are viable. This assumes that the nucleotide sequence of Actb is important and not the specific amino acid sequence of the protein it encodes. Upregulation of other actin paralogs was frequently observed upon β‐actin ablation and can also engage in the phenotype. For a better understanding, it will be necessary to analyze in current and future models all relevant actin transcripts and protein levels in a standardized and comprehensive way.

中文翻译:

是时候重新思考不同的 β-actin 转基因小鼠模型了吗?

肌动蛋白家族对许多细胞过程至关重要,在哺乳动物中存在肌肉和非肌肉形式。后一组包含细胞质-β-肌动蛋白和细胞质-γ-肌动蛋白,它们的氨基酸序列几乎相同并且具有显着的功能重叠。我们介绍了Actb基因和 mRNA 转录本的特性,主要关注 3'UTR 及其独特特征,即邮政编码和两个多聚腺苷酸化位点产生不同长度的转录本。已经创建了几种具有修饰的Actb基因座的转基因小鼠模型。不同的鼠标模型可以分为三组;即,5' 或 3' 插入模型,在外显子 2-3 周围具有 loxP 序列导致起始密码子缺失的小鼠模型,以及具有基因编辑Actb 的模型产生γ-肌动蛋白而不是β-肌动蛋白的序列。全身敲除和插入模型导致胚胎致死,这表明Actb基因或转录本或翻译的 β-肌动蛋白是必不可少的,但有一个例外,插入模型除外。发育后期的组织特异性消融导致无表型或轻度表型,这表明Actb基因或 β-肌动蛋白在某种程度上是可有可无的。产生γ-肌动蛋白的基因编辑的Actb小鼠是可行的。这假设Actb的核苷酸序列重要而不是它编码的蛋白质的特定氨基酸序列。在 β-肌动蛋白消融时经常观察到其他肌动蛋白旁系同源物的上调,也可以参与表型。为了更好地理解,有必要在当前和未来的模型中以标准化和全面的方式分析所有相关的肌动蛋白转录物和蛋白质水平。
更新日期:2021-01-06
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