title: Generation of a tamoxifen inducible SMN mouse for temporal SMN replacement.
abstract: Proximal spinal muscular atrophy (SMA) is caused by low levels of the SMN protein, encoded by the Survival Motor Neuron genes (SMN1 and SMN2). Mouse models of SMA can be rescued by increased SMN expression, but the timing of SMN replacement for complete rescue is unknown. Studies in zebrafish predict restoration of SMN function during embryogenesis may be important for axonal pathfinding, while the mouse models and normal human disease progression suggest that post-natal treatment may be sufficient for amelioration of disease. To evaluate the timing for SMN replacement, we have generated a stably integrated Cre-inducible SMN mouse in which expression of full-length SMN2 occurs after tamoxifen administration. Our temporally inducible SMN transgene is able to express SMN in embryonic, neonatal, and weanling mice and as such can be utilized in severe and mild SMA mouse models to identify the therapeutic window for SMN replacement.
authors.affiliation: The Center for Childhood Cancer, The Research Institute at Nationwide Children's Hospital, and the Department of Pediatrics, The Ohio State University, Columbus, Ohio 43205, USA.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Bebee
authors.forename: Jordan T
authors.initials: JT
authors.lastname: Gladman
authors.forename: Dawn S
authors.initials: DS
authors.lastname: Chandler
mesh_terms: D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005091:Exons; D005260:Female; D005838:Genotype; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009134:Muscular Atrophy, Spinal / Q000235:genetics / Q000503:physiopathology*; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics* / Q000378:metabolism; D013629:Tamoxifen / Q000008:administration & dosage*; D019076:Transgenes / Q000235:genetics
chemical_list: C526472:Smn1 protein, mouse; D055533:Survival of Motor Neuron 1 Protein; D013629:Tamoxifen