Obesity is a global health problem mainly attributed to environmental and lifestyle factors such as diet, low physical activity or socioeconomic factors. However, genetic factors also considerably contribute to weight-gain susceptibility. Although large-scale population genomic studies in humans have identified >1,000 loci associated with body mass index, effectively narrowing down candidate genes

Aripiprazole, a third-generation antipsychotic, acts as a dopamine partial agonist and is generally better tolerated than older antipsychotics by humans. However, many patients report gastrointestinal side effects, the mechanisms of which remain unclear. A study in Disease Models & Mechanisms used Drosophila melanogaster to model the potential gut toxicity of aripiprazole, exploring the conserved drug

Duchenne muscular dystrophy (DMD) is a severe, progressive muscle-wasting disease caused by mutations in the DMD gene, leading to a lack of dystrophin—a protein essential for stabilizing muscle cell membranes. The absence of dystrophin results in repeated muscle damage, degeneration and chronic inflammation. The canine model identified and characterized in 1988 remains the most widely used large-animal

Bovine tuberculosis (BTB), primarily caused by Mycobacterium bovis, is an important animal health and economic problem for the cattle industry and a potential zoonotic threat. Large animal models present practical and ethical limitations, calling for alternative experimental models to study BTB pathogenesis and identify therapies. In a new study in Communications Biology, researchers from the National

The axolotl, which can regenerate injuries to the central and peripheral nervous system, is an emerging model system to study neural circuit regeneration. Most findings in this model come from using classical tracers and imaging techniques, which present important limitations. Therefore, there is a need for new tools to efficiently label and/or manipulate cells in the axolotl nervous system and capture

Cardiomyopathies (CMs), including dilated, hypertrophic and left-ventricular noncompaction types, are common yet poorly understood myocardial diseases in children, with genetic factors explaining only a third of cases. A study in Disease Models & Mechanisms investigates the role of Rho/Rac guanine nucleotide exchange factor 18 (Arhgef18), a gene previously identified as having a potential role in CM

Obsessive-compulsive disorder (OCD) is a disabling psychiatric condition affecting up to 3% of the population, marked by intrusive thoughts and compulsive behaviors. Current treatments, such as selective serotonin reuptake inhibitors, are not universally effective. OCD pathology is linked to hyperactivity in corticostriatal-thalamic circuits and elevated glutamate:GABA ratios in brain regions like

In vertebrates, which harbor a closed circulatory system, intracardiac valves regulate the directionality of blood flow and valve failure or dysfunction can result in diminished heart functionality. Compared to vertebrates, invertebrate hearts exhibit rather simple valves. In Drosophila, which like all insects, has an open circulatory system, each valve consists of two contralaterally located cells

A recent study introduces a new method to quantify amyloid-β plaques in whole brains of mice to elucidate the variability in expressivity of a transgene widely used in Alzheimer’s disease research. The findings uncover a previously unrecognised imprinted pattern of transgene expression. This work highlights the importance of using in situ measurements that capture whole organs to reduce sampling errors

Duchenne muscular dystrophy (DMD) is a severe X-linked neuromuscular disorder caused by mutations in the DMD gene, affecting muscle function and leading to progressive decline and early mortality. The DMD gene gives rise to many dystrophin isoforms, of which multiple are expressed in the brain. While dystrophin isoforms like Dp427 and Dp140 are known to impact both muscle and brain function, their

Proprotein convertase subtilisin/kexin type 9 (PCSK9), encoded by the PCSK9 gene, is an enzyme produced and secreted by hepatocytes. PCSK9 promotes the degradation of low-density lipoprotein receptor (LDLR), which reduces LDLR density on the surface of hepatocytes and therefore impedes the ability to remove LDL particles from the blood. Gain-of-function PCSK9 mutations are causative of familial hypercholesterolemia

Multiple sclerosis (MS) is a central nervous system autoimmune condition in which damage to myelin causes symptoms like muscle weakness and vision changes. The precise cause of MS remains unclear; clinically relevant models are therefore needed to study MS-like lesions and develop treatments. In a new study published in Science, researchers used a marmoset experimental autoimmune encephalitis (EAE)

Refinement of procedures to minimize animal suffering is not only an ethical but also a legal requirement in animal research. In mouse models of sepsis, body temperature measurements are commonly used as a metric to keep track of animal overall health and monitor the status of disease progression. Traditional temperature tracking, while essential for assessing health and disease progression, often

Friedreich’s ataxia (FA) is an autosomal recessive disorder caused by a GAA expansion in the frataxin (Fxn) gene, leading to progressive cerebellar ataxia. Mouse models fail to fully replicate the progression of FA seen in humans, limiting therapeutic testing. A study in Disease Models & Mechanisms assessed muscular dexterity loss and peripheral sensation decline in the TG+ mouse, a mouse model with

Endometriosis—defined as the presence of the endometrium outside the uterine cavity—is a common disease affecting 5–10% of women of reproductive age globally. Among other symptoms, endometriosis can cause chronic pelvic pain, painful periods and infertility, which negatively impact the women’s quality of life. The exact cause of endometriosis is unclear, calling for more research to identify the mechanisms

Synucleinopathies such as Parkinson’s disease are neurodegenerative diseases characterized by the abnormal accumulation of α-synuclein (α-syn) aggregates in the peripheral and central nervous systems. Although accumulating evidence indicates higher prevalence, incidence of α-synucleinopathy and increased disease severity in men compared with women, few studies have documented the influence of sex on

Exercise is known to positively impact overall health, including through positive impacts in the brain. Exercise might induce its neuroprotective effect by regulating inflammation and plasticity through microglia and perineuronal net (PNN) expression. However, most studies rely on male-only mice data, leaving unexplored the effect of sex. A study in Behavioral Brain Research explores the effects of

Despite increasing evidence that intermittent fasting (IF) has beneficial effects on metabolic health, few studies have investigated whether the impact of IF is age dependent. A new study investigating the effects of IF on young (2-month-old), middle-aged (8-month-old) and old (18-month-old) male C57BL/6N mice reveals that age influences the effects of IF on glucose homeostasis. More precisely, while

Chronic pain is a growing concern, and hydrogen sulfide (H2S) has been identified as a potential modulator of pain. However, the mechanism behind H2S’s role in inflammation and pain regulation remains unclear. A study in Scientific Reports explores the relationship between H2S and astrocytes, known for their supportive role in synaptic function, exploring possible strategies for treating chronic pain

Methylene blue (MB) is a commonly used antifungal agent in zebrafish research, especially during early development (0–5 days post-fertilization (dpf)). Most guidelines, including the ones from the Federation of European Laboratory Animal Science Associations, recommend the use of 0.00005% or 0.0001% of MB for embryo/larval rearing. However, this practice overlooks the potential effects of MB on zebrafish

Obesity, or being overweight, increases lipid accumulation in the liver and leads to liver metabolic disorders. The liver has a critical role in controlling both lipid and glucose concentrations. Caloric restriction and/or increased protein content in a diet has been shown to improve liver lipid levels in rats. However, it is unknown if the beneficial effects of increased dietary protein on rodent

Sickle cell disease (SCD) is an inherited hematological disorder with a poorly characterized mechanism of metabolic dysregulation that is behind the disease progression. SCD induces hemolysis and oxidative stress and increases the consumption of cysteine for glutathione synthesis. Under extreme oxidative stress conditions, or when the endogenous cystine, reduced to produce cysteine, is restricted or

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, accounting for 75–85% of cases. Several animal models, including genetically modified mouse models, are available to study HCC pathogenesis and test new therapies. However, these models have major limitations, including differences in size, metabolic rate and drug metabolism compared to humans. To circumvent these limitations

Dimethoate, despite being banned in Europe and the UK, is still one of the most extensively used organophosphorus pesticides. Therefore, humans have a substantial risk of being exposed to and consuming the xenobiotic. Consequently, it is important to know the potential toxicity effects associated with oral intake of sublethal doses of dimethoate. A study in Scientific Reports studied the effects of

Animal models such as rodents and ferrets have been instrumental in understanding SARS-CoV-2 pathogenesis and transmission and in developing counteracting measures. However, most of these models present limitations to studying severe disease. Nonhuman primates (NHPs) are the most comparable model to human infections, but they are expensive and restricted to a few institutions worldwide. Pigs represent

The functional characterization of proteins during temporally constrained periods of mammalian development and disease is largely limited by the inability to rapidly and reversibly perturb their function. A new study addresses this challenge by directly comparing two targeted protein degradation systems in mice. These systems enable precise temporal degradation of proteins, offering unprecedented opportunities

Although increasing evidence suggests that the sex hormone estrogen (E2) is associated with alcohol consumption in humans, the underlying mechanisms have not been fully characterized. A study in mice provides new insights into these mechanisms by showing that E2 exerts its pro-drinking effects by activating neurons in the bed nucleus of the stria terminalis (BNST). The investigators exposed male and

Olfaction is one of the major senses and one of the first to develop along the evolutionary line. This sense has a major role in survival needs, like finding food or a suitable mate. With olfaction having a critical role in the assessment of external inputs, a new study in the Journal of Experimental Biology enquired whether it also has a role in regulating internal processes in Drosophila melanogaster

In vitro fertilization (IVF) is a reproductive method that assists in overcoming infertility. Besides the clinical setting, IVF is also used to support the production of laboratory animals for life science research. However, it is necessary to further improve the fertility rates and the success of the technique. A study in Biology of Reproduction analyzes the effect of the redox state of thiol groups

Reproductive aging in biological women is characterized by a progressive decline of ovarian function that culminates in menopause. Fertility usually decreases after age 35 with more limited pregnancies after age 40, indicating that changes in the premenopausal female reproductive tract are already occurring that negatively impact reproductive success. A study in Communications Biology shows that structural

Food allergies are a common immune reaction where symptoms can range from a slight discomfort to life-threatening situations. Peach allergy is a common food allergy in both Japan and the Mediterranean area, and this allergy still does not have an available immunotherapy. A study in Scientific Reports studied the effects of supplementing the diet of CBA/J mice that were sensitized to peach peel extract

Tumor-associated macrophages (TAMs) are an essential component of the tumor microenvironment and are predominantly thought to have pro-tumor effects. Therefore, the development of imaging tracers targeting TAMs is important for tumor monitoring and therapeutic efficacy evaluation. A new study in PNAS reports the development of a nanobody-based immunotracer targeting CD163—a receptor predominantly expressed

Atopic dermatitis (AD) is a chronic inflammatory skin disease with known immunological alterations. Human patients with AD show a reduction of the activity of the transcription factor nuclear factor erythroid 2–related factor 2 (Nrf2) in their epidermis. However, the functional relevance of this change is still unknown. A study in Disease Models & Mechanisms used mice lacking fibroblast growth factor

Prenatal maternal stress (PNMS) is associated with adverse pregnancy outcomes and predicts poorer developmental and health outcomes in the offspring. Previous studies have shown that exposure to PNMS can affect the F1 generation by inducing epigenetic modifications such as DNA methylation (DNAm) and expression of short noncoding RNAs, such as microRNAs (miRNAs). If PNMS occurs during primordial germ

This Review evaluates various mouse and rat models of chronic kidney disease (CKD) that result from repeated low-dose cisplatin (RLDC) treatment while also discussing ethical considerations on the topic. Cisplatin can cause nephrotoxicity, and high doses of cisplatin can cause acute kidney injury. The RLDC regimen has been used in the treatment of solid organ cancers and has shown efficacy in reducing

Traumatic brain injury (TBI) is a common injury resulting from an impact to the head. At least 80% of all TBI cases are considered mild (mTBI), also commonly referred to as a concussion, and are more prevalent in infants and older adolescents. While aerobic exercise, such as running, is known to improve cardiovascular health and support cognitive recovery after mTBI, its specific effects on memory

Lysosomes are considered to be important for metabolic adaptations during starvation, but these data come almost exclusively from in vitro studies. A study in Scientific Reports analyzes the proteomic changes in several organs in mice starved for 6 or 24 hours. Starved mice lose weight and initiate ketone body synthesis, confirming starvation-induced catabolism. Lysosomal protein composition shifts

Adolescent e-cigarette use has increased rapidly in recent years, sparking concerns about the potential long-term consequences on brain development. In a new study, Henderson and colleagues used an e-Vape self-administration (EVSA) assay to compare vaping-related nicotine reinforcement between male and female adult and adolescent C57BL/6J mice before extracting the mouse brains to assess neuronal function

In the past decade, several machine learning methods have been used to build epigenetic, transcriptomic and other omics-based aging clocks that can predict the biological age of an organism. While these techniques represent powerful approaches to quantify aging and monitor the effectiveness of anti-aging interventions, they come with a variety of technical limitations that can restrict their use in

Chemotherapy-induced neuropathic pain (CINP) is a prevalent long-term health complication in survivors of pediatric cancer, often emerging later in life. Current analgesic treatments are ineffective, reflecting our lack of understanding of the mechanisms behind CINP. A study in Disease Models & Mechanisms shows that early exposure to cisplatin causes neuroinflammation and nociception mediated by monocytes

The surrounding environment has an important role in shaping an individual's development and overall health. Both environmental and genetic factors influence the likelihood of developing disorders and the severity of their symptoms. Environmental enrichment improves cognitive performance in zebrafish. However, the exact role of the environment in shaping behavioral phenotypes of externalizing disorders

Glucokinase (GCK) is an enzyme with a critical role in glucose homeostatic maintenance. GCK acts as a glucose sensor for insulin secretion in pancreatic β-cells and regulates glycogen synthesis in the liver. Although the enzyme is a promising target for the development of new antidiabetic drugs, no clinically useful drug is available. In a new study, researchers from the University of Innsbruck in

Mitochondria are cellular organelles with their own genome (mtDNA) that are involved in several biological processes such as energy metabolism and signal transduction. Increasing evidence indicates that mitochondria also have a critical role in innate immunity, but it is unclear how variation in mtDNA affects responses to infection. In a new study, researchers used a panel of fruit fly Drosophila melanogaster