Genetic modification technologies apply to both rat (1, 2) and mouse (3, 4), therefore, the choice of the most appropriate Precision Toxicology™ in vivo model can now be based purely on biology and the needs of the research or drug development program.
In vivo solutions available or in development
For drug development studies and as a model of human disease, the rat has many advantages over the mouse. The size of the rat enables serial blood draws, and enhances the ability to perform surgical procedures. The rat is more proportional in the size of organ substructures that affect drug administration to specific anatomical areas, ease of i.v. dosing and relevant routes of metabolism. When using high value rodent models such as humanized rodents in toxicity testing, hepatotoxicity and drug induced liver injury (DILI) or drug induced liver disease, it is essential for the cost effectiveness of the study to be able to conduct serial sampling in a single animal.
Information from more than 100 years of phenotyping experience is available. The rat has become a standardized physiological and toxicological model, particularly in the pharmaceutical industry. There is a wide range of strains supporting an extensive literature on comparative physiology and, more recently, comparative genomics. The range of models that are more suited than the mouse to the study of human disease, has been presented recently in great detail (5).
- Furushima et al. (2012) Insertional mutagenesis by a hybrid piggyBac and sleeping beauty transposon in the rat. Genetics.
- Shao et al. (2014) CRISPR/Cas-mediated genome editing in the rat via direct injection of one-cell embryos. Nature Protocols.
- Ding et al. (2005) Efficient transposition of the piggyBac (PB) transposon in mammalian cells and mice Cell.
- Yang et al. (2014) Generating genetically modified mice using CRISPR/Cas-mediated genome engineering. Nature Protocols.
- Iannaccone et al. (2009) Rats! Disease Models & Mechanisms.
Why Switch to a Humanized Rat
- Better predictability
- The rat is the preferred species in toxicology
- Larger sample volumes & easier surgeries
- Safety and efficacy in the same species
Discover Predictability with Humanized Models
- Predicting severe hepatic toxicity MISSED in TRADITIONAL MODELS (Xu et al. PLOS Med 2014)
- Pharmacokinetics and drug clearance PREDICTIVE in HUMANIZED RODENT MODELS (Zhang et al. Biopharm Biophys Res. Comm. 2005)
- DRUG-DRUG INTERACTION studies more RELEVANT in HUMANIZED MODELS (Granvil et al. Drug Metab. Dispos. 2003)
- Human specific metabolites RECAPITULATED in HUMANIZED MODELS but NOT TRADITIONAL MODELS (Chen et al. J Pharmacol. Exp. Ther. 2006)