title: Tol2 gene trap integrations in the zebrafish amyloid precursor protein genes appa and aplp2 reveal accumulation of secreted APP at the embryonic veins.
abstract: BACKGROUND
  The single spanning transmembrane amyloid precursor protein (APP) and its proteolytic product, amyloid-beta (Ab) peptide, have been intensely studied due to their role in the pathogenesis of Alzheimer's disease. However, the biological role of the secreted ectodomain of APP, which is also generated by proteolytic cleavage, is less well understood. Here, we report Tol2 red fluorescent protein (RFP) transposon gene trap integrations in the zebrafish amyloid precursor protein a (appa) and amyloid precursor-like protein 2 (aplp2) genes. The transposon integrations are predicted to disrupt the appa and aplp2 genes to primarily produce secreted ectodomains of the corresponding proteins that are fused to RFP.
  
  
  RESULTS
  Our results indicate the Appa-RFP and Aplp2 fusion proteins are likely secreted from the central nervous system and accumulate in the embryonic veins independent of blood flow.
  
  
  CONCLUSIONS
  The zebrafish appa and aplp2 transposon insertion alleles will be useful for investigating the biological role of the secreted form of APP.
authors.affiliation: Department of Genetics, Development and Cell Biology, Iowa State University, Ames, Iowa 50011, USA.
authors.forename: Hsin-Kai
authors.initials: HK
authors.lastname: Liao
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Kristin E
authors.initials: KE
authors.lastname: Noack Watt
authors.forename: Qin
authors.initials: Q
authors.lastname: Wen
authors.forename: Justin
authors.initials: J
authors.lastname: Breitbach
authors.forename: Chelsy K
authors.initials: CK
authors.lastname: Kemmet
authors.forename: Karl J
authors.initials: KJ
authors.lastname: Clark
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Ekker
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Essner
authors.forename: Maura
authors.initials: M
authors.lastname: McGrail
mesh_terms: D000483:Alleles; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D058227:Amyloidogenic Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004251:DNA Transposable Elements / Q000235:genetics; D005456:Fluorescent Dyes / Q000378:metabolism; D005821:Genetic Techniques; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D016254:Mutagenesis, Insertional; D014680:Veins / Q000196:embryology / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*; D000097573:Red Fluorescent Protein
chemical_list: D016564:Amyloid beta-Protein Precursor; D058227:Amyloidogenic Proteins; D004251:DNA Transposable Elements; D005456:Fluorescent Dyes; D008164:Luminescent Proteins; D029961:Zebrafish Proteins; D000097573:Red Fluorescent Protein; C573648:Aplp2 protein, zebrafish; C573647:Appa protein, zebrafish