title: Generation of a conditional mouse model to target Acvr1b disruption in adult tissues.
abstract: Alk4 is a type I receptor that belongs to the transforming growth factor-beta (TGF-β) family. It takes part in the signaling of TGF-β ligands such as Activins, Gdfs, and Nodal that had been demonstrated to participate in numerous mechanisms ranging from early embryonic development to adult-tissue homeostasis. Evidences indicate that Alk4 is a key regulator of many embryonic processes, but little is known about its signaling in adult tissues and in pathological conditions where Alk4 mutations had been reported. Conventional deletion of Alk4 gene (Acvr1b) results in early embryonic lethality prior gastrulation, which has precluded study of Alk4 functions in postnatal and adult mice. To circumvent this problem, we have generated a conditional Acvr1b floxed-allele by flanking the fifth and sixth exons of the Acvr1b gene with loxP sites. Cre-mediated deletion of the floxed allele generates a deleted allele, which behaves as an Acvr1b null allele leading to embryonic lethality in homozygous mutant animals. A tamoxifen-inducible approach to target disruption of Acvr1b specifically in adult tissues was used and proved to be efficient for studying Alk4 functions in various organs. We report, therefore, a novel conditional model allowing investigation of biological role played by Alk4 in a variety of tissue-specific contexts.
authors.affiliation: Inserm U1052, Centre de Recherche en Cancérologie de Lyon, F-69000 Lyon, France.
authors.forename: Doriane
authors.initials: D
authors.lastname: Ripoche
authors.forename: Johann
authors.initials: J
authors.lastname: Gout
authors.forename: Roxane M
authors.initials: RM
authors.lastname: Pommier
authors.forename: Rami
authors.initials: R
authors.lastname: Jaafar
authors.forename: Chang X
authors.initials: CX
authors.lastname: Zhang
authors.forename: Laurent
authors.initials: L
authors.lastname: Bartholin
authors.forename: Philippe
authors.initials: P
authors.lastname: Bertolino
mesh_terms: D000483:Alleles; D000818:Animals; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005091:Exons; D005786:Gene Expression Regulation / Q000187:drug effects; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D009154:Mutation; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: C080034:Acrv1 protein, mouse; D008565:Membrane Proteins; D013629:Tamoxifen