PUBLICATION

Tol2 gene trap integrations in the zebrafish amyloid precursor protein genes appa and aplp2 reveal accumulation of secreted APP at the embryonic veins

Authors
Liao, H.K., Wang, Y., Watt, K.E., Wen, Q., Breitback, J., Kemmet, C.K., Clark, K.J., Ekker, S.C., Essner, J.J., and McGrail, M.
ID
ZDB-PUB-120127-5
Date
2012
Source
Developmental Dynamics : an official publication of the American Association of Anatomists   241(2): 415-425 (Journal)
Registered Authors
Clark, Karl, Ekker, Stephen C., Essner, Jeffrey, McGrail, Maura
Keywords
Tol2 gene trap, endothelial cells, vein, vasculature, central nervous system
MeSH Terms
  • Alleles
  • Amyloid beta-Protein Precursor/genetics
  • Amyloid beta-Protein Precursor/metabolism*
  • Amyloidogenic Proteins/genetics
  • Amyloidogenic Proteins/metabolism*
  • Animals
  • DNA Transposable Elements/genetics
  • Fluorescent Dyes/metabolism
  • Genetic Techniques
  • Luminescent Proteins/genetics
  • Luminescent Proteins/metabolism
  • Mutagenesis, Insertional
  • Veins/embryology
  • Veins/metabolism
  • Zebrafish/embryology*
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
22275008 Full text @ Dev. Dyn.
Abstract

Background: The single spanning transmembrane amyloid precursor protein (APP) and its proteolytic product, amyloid-beta (Aβ) 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.

Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping