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Time for rethinking the different U+03B2U+2010actin transgenic mouse models?
Tijdschriftbijdrage - Review Artikel
The actin family is crucial for many cellular processes and in mammals muscle and non-muscle forms exist. The latter group contains cytoplasmic-beta-actin and cytoplasmic-gamma-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 gamma-actin protein instead of beta-actin. Whole body knockouts and, with one exception, insertion models lead to embryonic lethality indicating that the Actb gene or transcripts or translated beta-actin are essential. Tissue specific ablation at later developmental stages lead to no, or mild phenotypes, suggesting that the Actb gene or beta-actin protein is somewhat dispensable. Gene edited Actb mice that produce gamma-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 beta-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.
Pagina's: 527 - 543
Jaar van publicatie:2020