ArticleNucleic acids research2006
Transcriptional and phenotypic comparisons of Ppara knockout and siRNA knockdown mice.
Article in Nucleic acids research, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed.
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- Pathway-driven analysis of synthetic lethal interactions in cancer using perturbation screens.Life science alliance · 2024Article
- Knockout of STE20-type kinase TAOK3 does not attenuate diet-induced NAFLD development in mice.Molecular medicine (Cambridge, Mass.) · 2023Article
- Transposon sequencing identifies genes impactingInfection and immunity · 2023Article
- Rethinking the Architecture of Attachment: New Insights into the Role for Oxytocin Signaling.Affective science · 2022Review
- Exon-dependent transcriptional adaptation by exon-junction complex proteins Y14/RNP-4 and MAGOH/MAG-1 in Caenorhabditis elegans.PLoS genetics · 2022Article
- TRIM28 Is a Novel Regulator of CD133 Expression Associated with Cancer Stem Cell Phenotype.International journal of molecular sciences · 2022Article
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- Genotype to Phenotype: CRISPR Gene Editing Reveals Genetic Compensation as a Mechanism for Phenotypic Disjunction of Morphants and Mutants.International journal of molecular sciences · 2021Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors.
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No grant is acknowledged in the PubMed record.
Abstract
RNA interference (RNAi) has great potential as a tool for studying gene function in mammals. However, the specificity and magnitude of the in vivo response to RNAi remains to be fully characterized. A molecular and phenotypic comparison of a genetic knockout mouse and the corresponding knockdown version would help clarify the utility of the RNAi approach. Here, we used hydrodynamic delivery of small interfering RNA (siRNA) to knockdown peroxisome proliferator activated receptor alpha (Ppara), a gene that is central to the regulation of fatty acid metabolism. We found that Ppara knockdown in the liver results in a transcript profile and metabolic phenotype that is comparable to those of Ppara-/- mice. Combining the profiles from mice treated with the PPARalpha agonist fenofibrate, we confirmed the specificity of the RNAi response and identified candidate genes proximal to PPARalpha regulation. Ppara knockdown animals developed hypoglycemia and hypertriglyceridemia, phenotypes observed in Ppara-/- mice. In contrast to Ppara-/- mice, fasting was not required to uncover these phenotypes. Together, these data validate the utility of the RNAi approach and suggest that siRNA can be used as a complement to classical knockout technology in gene function studies.
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