INFRAFRONTIER quality principles in systemic phenotyping.

Improving reproducibility and replicability in preclinical research is a widely discussed and pertinent topic, especially regarding ethical responsibility in animal research. INFRAFRONTIER, the European Research Infrastructure for the generation, phenotyping, archiving, and distribution of model mammalian genomes, is addressing this issue by developing internal quality principles for its different service areas, that provides a quality framework for its operational activities. This article introduces the INFRAFRONTIER Quality Principles in Systemic Phenotyping of genetically altered mouse models. A total of 11 key principles are included, ranging from general requirements for compliance with guidelines on animal testing, to the need for well-trained personnel and more specific standards such as the exchange of reference lines. Recently established requirements such as the provision of FAIR (Findable, Accessible, Interoperable, Reusable) data are also addressed. For each quality principle, we have outlined the specific context, requirements, further recommendations, and key references.

Microglia-specific knock-down of Bmal1 improves memory and protects mice from high fat diet-induced obesity.

Microglia play a critical role in maintaining neural function. While microglial activity follows a circadian rhythm, it is not clear how this intrinsic clock relates to their function, especially in stimulated conditions such as in the control of systemic energy homeostasis or memory formation. In this study, we found that microglia-specific knock-down of the core clock gene, Bmal1, resulted in increased microglial phagocytosis in mice subjected to high-fat diet (HFD)-induced metabolic stress and likewise among mice engaged in critical cognitive processes. Enhanced microglial phagocytosis was associated with significant retention of pro-opiomelanocortin (POMC)-immunoreactivity in the mediobasal hypothalamus in mice on a HFD as well as the formation of mature spines in the hippocampus during the learning process. This response ultimately protected mice from HFD-induced obesity and resulted in improved performance on memory tests. We conclude that loss of the rigorous control implemented by the intrinsic clock machinery increases the extent to which microglial phagocytosis can be triggered by neighboring neurons under metabolic stress or during memory formation. Taken together, microglial responses associated with loss of Bmal1 serve to ensure a healthier microenvironment for neighboring neurons in the setting of an adaptive response. Thus, microglial Bmal1 may be an important therapeutic target for metabolic and cognitive disorders with relevance to psychiatric disease.