A Noninvasive Ocular (Tear) Sampling Method for Genetic Ascertainment of Transgenic Mice and Research Ethics Innovation.

ABSTRACT

Animal models, animal welfare and research ethics are both facilitators and gatekeepers for Big Data generation in genomics and multi-omics R&D. Safeguarding animal welfare is also a research ethics issue that can benefit from technical innovations in biosample collection in particular. Animal welfare draws from the guiding principles of 3R, namely, "Replacement" (methods avoiding the use of animals in research), "Reduction" (methods using fewer animals or derive more information from the same number of animals), and "Refinement" (methods removing or minimizing pain or distress). We report here that noninvasive ocular (tear) sampling for genetic ascertainment of transgenic mice can serve as an innovative ethical safeguard for animal welfare, and as a veritable alternative to the surgical tail biopsies, ear puncture, or blood sampling from the weanling transgenic mice. We compared ocular versus tail biopsy sampling in regard to ascertainment, by genotyping, of apolipoprotein E-deficient (ApoE-/-) transgenic weanling mice (n = 60) by one-round polymerase chain reaction analysis. We found that ocular sampling compares to the results obtained by tail sampling with the obvious benefit of being noninvasive and improving the 3R, especially for the Refinement principle of animal welfare. To place the importance of this new biosample collection approach into further context, transgenic mice research and animal models are at the epicenter of Big Data translation to health innovation. We suggest that ocular sampling is considered and evaluated further in transgenic mice models, not to mention warrant exploration for applications in other types of animal models that require noninvasive biosample collection.