title: A new gain-of-function mouse line to study the role of Wnt3a in development and disease.
abstract: Wnt/β-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 β-catenin/Tcf-Lef reporter and of the universal Wnt/β-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) (β-catenin(GOF) ) mutants. These data indicate that the exogenously expressed Wnt3a stimulates the Wnt/β-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.
authors.affiliation: Cancer and Developmental Biology Laboratory, Center for Cancer Research, NCI-Frederick, NIH, Frederick, Maryland, 21702.
authors.forename: Ravindra B
authors.initials: RB
authors.lastname: Chalamalasetty
authors.affiliation: Mammalian Development Laboratory, National Institute of Genetics, Mishima, Shizouka, 411-8540, Japan.
authors.forename: Rieko
authors.initials: R
authors.lastname: Ajima
authors.affiliation: Cancer and Developmental Biology Laboratory, Center for Cancer Research, NCI-Frederick, NIH, Frederick, Maryland, 21702.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Garriock
authors.affiliation: Cancer and Developmental Biology Laboratory, Center for Cancer Research, NCI-Frederick, NIH, Frederick, Maryland, 21702.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Kennedy
authors.affiliation: Mouse Cancer Genetics Program, Center for Cancer Research, NCI-Frederick, NIH, Frederick, Maryland, 21702.
authors.forename: Lino
authors.initials: L
authors.lastname: Tessarollo
authors.affiliation: Cancer and Developmental Biology Laboratory, Center for Cancer Research, NCI-Frederick, NIH, Frederick, Maryland, 21702. yamagute@mail.nih.gov.
authors.forename: Terry P
authors.initials: TP
authors.lastname: Yamaguchi
mesh_terms: D000818:Animals; D018390:Gene Targeting / Q000379:methods*; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000235:genetics; D019426:Integrases / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D019076:Transgenes; D015854:Up-Regulation; D060509:Wnt3A Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse; C045073:Cre recombinase; D019426:Integrases
keywords: Wnt3a; development; gastrulation; growth factor; mouse embryo; presomitic mesoderm (PSM); primitive streak (PS); stem cells