Head of the Transgenic Core Facility
Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Dresden, Germany
Ronald has been working with laboratory animals since 1995, and in 2002 he established the Transgenic Core Facility at the MPI-CBG. In 2022, Ronald Naumann and Peter Dobrowolski received the 3R ISTT Prize for the technical development of STR analysis. He has been involved in setting up many facilities worldwide and supports other scientific institutions with his experience.
For over four decades, thousands of mice have been produced during germline transmission in the production of mutant mouse lines via ES cell injections. All offspring are tested for the desired mutation. Frequently, despite intensive breeding, no germline transmission occurs. All negative offspring are euthanized. This contradicts the 3Rs (Reduction, Replacement, Refinement), which must be taken into account in experimental science. Our new method of pre-analyzing sperm from chimeras using short tandem repeat (STR) markers and subsequent IVF represents a fast and safe method (STR-IVF) to generate the heterozygous F1 generation with a significantly lower number of animals. STR analysis of chimeric sperm works with all common ES cell backgrounds and with all inbred mouse donor backgrounds. The use of this technology has prevented the unnecessary production—and subsequent euthanasia—of approximately 5,600 animals over the past four years.
The origin of the idea, this technology, and reduction in animals comes from this publication:
Novel insights into the genetic background of genetically modified mice – Dobrowolski, Fischer, Naumann, Transgenic Res . 2018
The 3Rs Implementation Award was generously sponsored by Charles River.
Work conducted at Sanofi
Research Summary: When developing new medicines, animal studies are often used to identify potential safety risks. However, these risks do not always translate to humans. In this work, we investigated liver toxicity seen in dogs during pre-clinical testing of amcenestrant, a drug being developed for breast cancer. To understand whether this liver toxicity was relevant to humans, we used 3D liver spheroids, generated from human, dog, and rat hepatic cells. These liver spheroids mimic species-specific liver function and allowed us to study drug effects without additional animal studies. We discovered that amcenestrant disrupted key metabolic liver pathways in dogs, specifically, those involved in bile acid regulation leading to liver damage. In contrast, human liver spheroids showed no such disruption, and these findings were corroborated by the lack of liver findings in clinical trials with amcenestrant . This work showed that dogs are uniquely sensitive to amcenestrant due to species-specific biology. Further in vivo studies in dogs were avoided by using the liver spheroids to understand the mechanism of action of amcenestrant-induced liver injury in the dog and its lack of relevance to humans. This work supports the principles of the 3Rs – Replacement, Reduction, and Refinement by using human-relevant models to improve drug safety and reduce reliance on animal testing.
The Building Bridges Award was generously sponsored by Biomere.