title: Knockdown of amyloid precursor protein in zebrafish causes defects in motor axon outgrowth.
abstract: Amyloid precursor protein (APP) plays a pivotal role in Alzheimer's disease (AD) pathogenesis, but its normal physiological functions are less clear. Combined deletion of the APP and APP-like protein 2 (APLP2) genes in mice results in post-natal lethality, suggesting that APP performs an essential, if redundant, function during embryogenesis. We previously showed that injection of antisense morpholino to reduce APP levels in zebrafish embryos caused convergent-extension defects. Here we report that a reduction in APP levels causes defective axonal outgrowth of facial branchiomotor and spinal motor neurons, which involves disorganized axonal cytoskeletal elements. The defective outgrowth is caused in a cell-autonomous manner and both extracellular and intracellular domains of human APP are required to rescue the defective phenotype. Interestingly, wild-type human APP rescues the defective phenotype but APPswe mutation, which causes familial AD, does not. Our results show that the zebrafish model provides a powerful system to delineate APP functions in vivo and to study the biological effects of APP mutations.
authors.affiliation: Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Ping
authors.initials: P
authors.lastname: Song
authors.forename: Sanjay W
authors.initials: SW
authors.lastname: Pimplikar
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000627:therapeutic use; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006801:Humans; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology*; D009154:Mutation; D010641:Phenotype; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*
chemical_list: D016564:Amyloid beta-Protein Precursor