Time for rethinking the different β-actin transgenic mouse models?

Area of Science:

• Cell Biology
• Genetics
• Molecular Biology

Background:

• The actin family is vital for cellular functions, with mammals having muscle and non-muscle forms.
• Cytoplasmic-β-actin (Actb) and cytoplasmic-γ-actin are highly similar, sharing functional roles.

Purpose of the Study:

• To investigate the properties of the Actb gene and its mRNA transcripts, focusing on the 3'UTR.
• To analyze the essentiality of Actb and β-actin protein using various transgenic mouse models.

Main Methods:

• Creation of transgenic mouse models with modified Actb loci (insertion, deletion, gene editing).
• Analysis of phenotypes resulting from whole-body knockouts, tissue-specific ablation, and gene editing.
• Examination of β-actin ablation effects and upregulation of other actin paralogs.

Main Results:

• Whole-body Actb knockouts and most insertion models result in embryonic lethality.
• Tissue-specific ablation of Actb shows mild or no phenotypes, indicating dispensability later in development.
• Gene-edited mice producing γ-actin instead of β-actin are viable, suggesting nucleotide sequence importance.

Conclusions:

• The Actb gene and its transcripts are crucial for embryonic viability.
• β-actin protein may be dispensable in later developmental stages, with potential compensation by other actin paralogs.
• Further comprehensive analysis of actin transcripts and protein levels is needed to understand functional redundancy.