PUBLICATION
Early embryonic gene expression profiling of zebrafish prion protein (prp2) morphants
- Authors
- Nourizadeh-Lillabadi, R., Seilø Torgersen, J., Vestrheim, O., König, M., Aleström, P., and Syed, M.
- ID
- ZDB-PUB-101108-21
- Date
- 2010
- Source
- PLoS One 5(10): e13573 (Journal)
- Registered Authors
- Aleström, Peter, König, Melanie, Nourizadeh-Lillabadi, Rasoul
- Keywords
- none
- MeSH Terms
-
- 5' Untranslated Regions
- Animals
- Base Sequence
- DNA
- Fluorescent Antibody Technique
- Gene Expression Profiling*
- Gene Expression Regulation, Developmental*
- Molecular Sequence Data
- Prions/genetics*
- Reverse Transcriptase Polymerase Chain Reaction
- Zebrafish
- PubMed
- 21042590 Full text @ PLoS One
Citation
Nourizadeh-Lillabadi, R., Seilø Torgersen, J., Vestrheim, O., König, M., Aleström, P., and Syed, M. (2010) Early embryonic gene expression profiling of zebrafish prion protein (prp2) morphants. PLoS One. 5(10):e13573.
Abstract
BACKGROUND: The Prion protein (PRNP/Prp) plays a crucial role in transmissible spongiform encephalopathies (TSEs) like Creutzfeldt-Jakob disease (CJD), scrapie and mad cow disease. Notwithstanding the importance in human and animal disease, fundamental aspects of PRNP/Prp function and transmission remains unaccounted for.
METHODOLOGY/PRINCIPAL FINDINGS: The zebrafish (Danio rerio) genome contains three Prp encoding genes assigned prp1, prp2 and prp3. Currently, the second paralogue is believed to be the most similar to the mammalian PRNP gene in structure and function. Functional studies of the PRNP gene ortholog was addressed by prp2 morpholino (MO) knockdown experiments. Investigation of Prp2 depleted embryos revealed high mortality and apoptosis at 24 hours post fertilization (hpf) as well as impaired brain and neuronal development. In order to elucidate the underlying mechanisms, a genome-wide transcriptome analysis was carried out in viable 24 hpf morphants. The resulting changes in gene expression profiles revealed 249 differently expressed genes linked to biological processes like cell death, neurogenesis and embryonic development.
CONCLUSIONS/SIGNIFICANCE: The current study contributes to the understanding of basic Prp functions and demonstrates that the zebrafish is an excellent model to address the role of Prp in vertebrates. The gene knockdown of prp2 indicates an essential biological function for the zebrafish ortholog with a morphant phenotype that suggests a neurodegenerative action and gene expression effects which are apoptosis related and effects gene networks controlling neurogenesis and embryo development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping