title: Genetically engineered mouse models to evaluate the role of Wnt secretion in bone development and homeostasis.
abstract: Alterations in components of the Wnt signaling pathway are associated with altered bone development and homeostasis in several human diseases. We created genetically engineered mouse models (GEMMs) that mimic the cellular defect associated with the Porcupine mutations in patients with Goltz Syndrome/Focal Dermal Hypoplasia. These GEMMs were established by utilizing mice containing a conditionally inactivatable allele of Wntless/GPR177 (a gene encoding a protein required for the transport of Porcupine-modified ligand to the plasma membrane for secretion). We crossed this strain to another which drives cre-mediated gene deletion in mature osteoblasts (Osteocalcin-cre) resulted in mice lacking the ability to secrete Wnt ligands in this cell type. These mice displayed severely reduced bone mass and provide a model to understand the effects of disrupting the ability to secrete Wnt ligands on the skeletal system.
authors.forename: Bart O
authors.initials: BO
authors.lastname: Williams
mesh_terms: D000217:Acyltransferases; D000818:Animals; D001846:Bone Development; D004195:Disease Models, Animal; D005489:Focal Dermal Hypoplasia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D005818:Genetic Engineering; D006706:Homeostasis; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D008565:Membrane Proteins; D051153:Wnt Proteins; D000217:Acyltransferases; C491188:PORCN protein, human
keywords: Wnt; Wntless/GPR177; bone; osteoblasts; porcupine