title: Generation of a conditional mutant allele for Tab1 in mouse.
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.
authors.affiliation: Department of Environmental and Molecular Toxicology, North Carolina State University, Raleigh, North Carolina, USA.
authors.forename: Maiko
authors.initials: M
authors.lastname: Inagaki
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komatsu
authors.forename: Greg
authors.initials: G
authors.lastname: Scott
authors.forename: Gen
authors.initials: G
authors.lastname: Yamada
authors.forename: Manas
authors.initials: M
authors.lastname: Ray
authors.forename: Jun
authors.initials: J
authors.lastname: Ninomiya-Tsuji
authors.forename: Yuji
authors.initials: Y
authors.lastname: Mishina
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000818:Animals; D005091:Exons; D018390:Gene Targeting; D019426:Integrases / Q000378:metabolism; D051379:Mice; D009154:Mutation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C531463:Tab1 protein, mouse; C045073:Cre recombinase; D019426:Integrases