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Publication : A new gain-of-function mouse line to study the role of Wnt3a in development and disease.

First Author  Chalamalasetty RB Year  2016
Journal  Genesis Volume  54
Issue  9 Pages  497-502
PubMed ID  27411055 Mgi Jnum  J:236315
Mgi Id  MGI:5805727 Doi  10.1002/dvg.22959
Citation  Chalamalasetty RB, et al. (2016) A new gain-of-function mouse line to study the role of Wnt3a in development and disease. Genesis 54(9):497-502
abstractText  Wnt/beta-catenin signals are important regulators of embryonic and adult stem cell self-renewal and differentiation and play causative roles in tumorigenesis. Purified recombinant Wnt3a protein, or Wnt3a-conditioned culture medium, has been widely used to study canonical Wnt signaling in vitro or ex vivo. To study the role of Wnt3a in embryogenesis and cancer models, we developed a Cre recombinase activatable Rosa26(Wnt3a) allele, in which a Wnt3a cDNA was inserted into the Rosa26 locus to allow for conditional, spatiotemporally defined expression of Wnt3a ligand for gain-of-function (GOF) studies in mice. To validate this reagent, we ectopically overexpressed Wnt3a in early embryonic progenitors using the T-Cre transgene. This resulted in up-regulated expression of a beta-catenin/Tcf-Lef reporter and of the universal Wnt/beta-catenin pathway target genes, Axin2 and Sp5. Importantly, T-Cre; Rosa26(Wnt3a) mutants have expanded presomitic mesoderm (PSM) and compromised somitogenesis and closely resemble previously studied T-Cre; Ctnnb1(ex3) (beta-catenin(GOF) ) mutants. These data indicate that the exogenously expressed Wnt3a stimulates the Wnt/beta-catenin signaling pathway, as expected. The Rosa26(Wnt3a) mouse line should prove to be an invaluable tool to study the function of Wnt3a in vivo.
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