The Rise of Three Rs Centres and Platforms in Europe*

Public awareness and discussion about animal experiments and replacement methods has greatly increased in recent years. The term 'the Three Rs', which stands for the Replacement, Reduction and Refinement of animal experiments, is inseparably linked in this context. A common goal within the Three Rs scientific community is to develop predictive non-animal models and to better integrate all available data from in vitro, in silico and omics technologies into regulatory decision-making processes regarding, for example, the toxicity of chemicals, drugs or food ingredients. In addition, it is a general concern to implement (human) non-animal methods in basic research. Toward these efforts, there has been an ever-increasing number of Three Rs centres and platforms established over recent years - not only to develop novel methods, but also to disseminate knowledge and help to implement the Three Rs principles in policies and education. The adoption of Directive 2010/63/EU on the protection of animals used for scientific purposes gave a strong impetus to the creation of Three Rs initiatives, in the form of centres and platforms. As the first of a series of papers, this article gives an overview of the European Three Rs centres and platforms, and their historical development. The subsequent articles, to be published over the course of ATLA's 50th Anniversary year, will summarise the current focus and tasks as well as the future and the plans of the Three Rs centres and platforms. The Three Rs centres and platforms are very important points of contact and play an immense role in their respective countries as 'on the ground' facilitators of Directive 2010/63/EU. They are also invaluable for the widespread dissemination of information and for promoting implementation of the Three Rs in general

The Current Status and Work of Three Rs Centres and Platforms in Europe*

The adoption of Directive 2010/63/EU on the protection of animals used for scientific purposes has given a major push to the formation of Three Rs initiatives in the form of centres and platforms. These centres and platforms are dedicated to the so-called Three Rs, which are the Replacement, Reduction and Refinement of animal use in experiments. ATLA's 50th Anniversary year has seen the publication of two articles on European Three Rs centres and platforms. The first of these was about the progressive rise in their numbers and about their founding history; this second part focuses on their current status and activities. This article takes a closer look at their financial and organisational structures, describes their Three Rs focus and core activities (dissemination, education, implementation, scientific quality/translatability, ethics), and presents their areas of responsibility and projects in detail. This overview of the work and diverse structures of the Three Rs centres and platforms is not only intended to bring them closer to the reader, but also to provide role models and show examples of how such Three Rs centres and platforms could be made sustainable. The Three Rs centres and platforms are very important focal points and play an immense role as facilitators of Directive 2010/63/EU 'on the ground' in their respective countries. They are also invaluable for the wide dissemination of information and for promoting the implementation of the Three Rs in general

Gender-dependent disease severity in autosomal polycystic kidney disease of rats.

The impact of gender on the course of chronic renal failure in polycystic kidney disease (PKD) has been under discussion for years. Recently an animal model of autosomal dominant PKD in the rat became available allowing this topic to be studied. The aim of this study was to evaluate disease severity according to gender, and the occurrence of anticipation and/or genetic imprinting. Male and female affected PKD rats were crossed with respective Wistar-Ottawa-Karlsburg (WOK) rats. From this P generation 26 affected F1 hybrids were obtained, which were then backcrossed with WOK rats, resulting in 275 backcrosses (BC generation). In BC rats the affected males had a significantly higher kidney weight, worse histology and poorer renal function than the females. In the male, but not the female rats of the BC generation, transmission from an affected F1 mother resulted in significantly higher kidney weight, worse histology and poorer renal function than when the gene was inherited through an affected father. Since at the same time body and kidney weight were higher in the respective unaffected males, the previous effect in the affected rats might be due to a growth factor transferred by the mother's milk. The sex of the P generation had no such impact on these parameters. Thus our data provide no evidence for disease anticipation and genetic imprinting (in the classical sense) in the PKD rats, and the assumption of a gender-dependent disease expressivity is favored