Generation of a conditional mutant allele for Tab1 in mouse
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Updated: Jul 2, 2026
Removal of an Internal Translational Start Site from mRNA While Retaining Expression of the Full-Length Protein
Published on: March 16, 2022
Maiko Inagaki1, Yoshihiro Komatsu, Greg Scott
1Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, North Carolina, USA.
Abstract:
TAK1 binding protein 1 (TAB1) binds and induces autophosphorylation of TGF-beta activating kinase (TAK1). TAK1, a mitogen-activated kinase kinase kinase, is involved in several distinct signaling pathways including non-Smad pathways for TGF-beta superfamily members and inflammatory responses caused by cytokines. Conventional disruption of the murine Tab1 gene results in late gestational lethality showing intraventricular septum defects and underdeveloped lung alveoli. To gain a better understanding of the roles of TAB1 in different tissues, at different stages of development, and in pathological conditions, we generated Tab1 floxed mice in which the loxP sites flank Exons 9 and 10 to remove the C-terminal region of TAB1 protein necessary for activation of TAK1. We demonstrate that Cre-mediated recombination using Sox2-Cre, a Cre line expressed in the epiblast during early embryogenesis, results in deletion of the gene and protein. These homozygous Cre-recombined null embryos display an identical phenotype to conventional null embryos. This animal model will be useful in revealing distinct roles of TAB1 in different tissues at different stages.
Insights
Researchers created new Tab1 floxed mice to study TAB1 protein roles. These mice models mimic conventional null embryos, enabling research into TAB1
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- TAK1 binding protein 1 (TAB1) is crucial for activating TAK1, a kinase involved in TGF-beta and inflammatory signaling pathways.
- Conventional knockout of the Tab1 gene leads to embryonic lethality with cardiac and lung developmental defects.
Purpose of the Study:
- To develop a conditional knockout mouse model for TAB1 to investigate its tissue-specific and stage-specific functions.
- To enable detailed study of TAB1's roles in various physiological and pathological contexts.
Main Methods:
- Generation of Tab1 floxed mice with loxP sites flanking critical exons (9 and 10).
- Utilized Sox2-Cre recombinase for early embryonic deletion of the Tab1 gene.
- Phenotypic analysis of homozygous Cre-recombined null embryos.
Main Results:
- Cre-mediated recombination successfully deleted the Tab1 gene and protein in Sox2-Cre expressing embryos.
- Homozygous null embryos exhibited phenotypes identical to conventionally generated Tab1 null embryos, including developmental defects.
- The generated floxed mouse model effectively recapitulates the conventional knockout phenotype.
Conclusions:
- The Tab1 floxed mouse model provides a valuable tool for studying the specific roles of TAB1 in different tissues and developmental stages.
- This model will facilitate research into the complex functions of TAB1 beyond embryonic lethality, particularly in distinct cellular environments and disease states.
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