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Despite centuries of effort from philosophers, physicians and biologists, the answer to the seemingly simple question “what is aging?” remains elusive. Some even posit that aging represents a phenomenon too expansive to ever be succinctly defined. A new study tackles this question by profiling hundreds of phenotypes across age in mice and examining how the trajectories of these phenotypes are altered by geroprotective genetic and dietary interventions.
A challenge in translational research is comparing behaviors across species. A new study combines a novel behavioral paradigm in rats and humans with reinforcement learning to infer shared computations for goal-directed navigation.
The application of genome-editing tools to generate point mutations in animal models is of particular value for precise disease modeling, but the PAM requirement of Cas enzymes is a critical limiting factor. Two new studies demonstrate that SpRY variant displays efficient genome editing in a nearly PAM-less manner in zebrafish, expanding the targeting scope of base editors in this model.
Single nucleotide polymorphisms in the FKBP5 gene influence the risk of developing stress-related disorders, but the underlying processes are not fully understood. Animal models offer a possibility to investigate the influence of FKBP5 gene variants on the stress response system.
New insights into gut-brain axis and cognition function show that accumulation of Caudovirales bacteriophages in the gut microbiota is associated with improved executive function and memory.
Rodent grooming is an important behaviour that is commonly used to characterize preclinical models of human brain disorders. A new paper has leveraged deep learning to develop a precise, high throughput and automated grooming classifier to facilitate mechanistic neuroscience research on grooming.
Social isolation can lead to poor mental and physical health. A new study determines that social isolation increases food and nicotine-seeking during abstinence, but that social housing can reverse these effects.
A new CRISPR/Cas9 method that can generate F0 mutant zebrafish has the potential to cut costs, spare time, and reduce animal use for researchers interested in screening loss-of-function alleles in vivo.
To achieve knockdown rather than knockout of particular genes, a new paper demonstrates a CRISPR/Cas13 method that can efficiently edit mRNA in zebrafish, medaka, killifish, and mouse embryos.
Cortico-striatal circuits are at the heart of many brain disorders, which means they are often studied using neurobiological animal models. A new study uses resting-state functional connectivity to assess homologies of cortico-striatal circuits in mice, monkeys, and humans.
Caged neurotransmitters are widely used to study neurobiological processes such as synaptic transmission and plasticity. However, uncaging has been primarily restricted to in vitro and ex vivo experimental systems. Using caged neurotransmitters in vivo has posed a huge hurdle because photoactivatable cages bind to GABA-A receptors, acting as competitive antagonists towards GABA. This reduced inhibition leads to epileptiform-like activity, which can cause problems for circuit level studies in vivo. To circumvent this off-target effect, a recent publication introduces a new caged glutamate: G5-MNI-glutamate. Using a novel technique called ‘cloaking,’ GABA-A receptor antagonism is abolished, opening up new possibilities for future in vivo studies with caged neurotransmitters.
Vasculature has an essential role both in central nervous system health and diseases. A new optimized imaging and analysis pipeline helps to characterize blood vessel network topology and plasticity across large regions in detail.
Human cancer is a disease of cooperating genetic events that is complex to model in vivo. A new study combines somatic base editing with a mouse model of breast cancer, demonstrating the potential to rapidly investigate the function of disease-specific point mutations.
Microglia play important but incompletely understood roles in the pathogenesis of neurological disease. New chimeric models using transplanted human stem cell-derived microglia-like cells hold great promise to better model the unique function of human microglia in brain disease.
With the genetics of a laboratory strain but a more diverse microbiome, ‘wildling’ mice could be a novel complement to commonly used specific pathogen-free animals in preclinical studies.
In medical research, treatments are often thought of as moving “from bench to bedside.” A new study identifies a specific treatment in zebrafish and brings it to a patient, highlighting the role of these animal models in personalized medicine.
The mammalian gut microbiota confers colonization resistance against pathogenic bacteria. Specific pathogen-free C57BL/6 mice from different vendors are variably resistant to oral non-typhoidal Salmonella infection. New work shows that differences in endogenous Enterobacteriaceae determine this phenotypic variability.
