Biology subjects

Wilson, R.

Publications and source records attributed to Wilson, R..

At least 19 recordsLinked to original sources

bioRxiv2026

Sustained Maternal Cortisol Elevation Links Metabolic Stress to Fetal Growth Restriction in a Guinea Pig Model of Undernutrition

Fetal growth restriction (FGR) resulting from maternal undernutrition is commonly attributed to insufficient nutrient substrate delivery to the fetus. However, the contribution of maternal physiological stress responses to this outcome remains poorly characterized. Using the well-established guinea pig maternal nutrient restriction (MNR) model, we conducted a comprehensive retrospective analysis to interrogate the hypothesis that maternal stress physiology actively mediates fetal growth outcomes beyond simple substrate limitation. Maternal salivary and serum cortisol were significantly elevated in MNR dams throughout pregnancy despite no baseline differences at conception, indicating that hypothalamic-pituitary-adrenal (HPA) axis activation was specifically triggered by the combined physiological demands of pregnancy and nutritional constraint. The sustained cortisol elevation was accompanied by acute metabolic perturbations at mid-pregnancy, including hypoglycemia and depleted circulating lipids. While most acute metabolic disturbances resolved by near-term, cortisol remained elevated, and MNR fetuses exhibited parallel cortisol elevation alongside sustained growth restriction. Maternal weight divergence emerged only in late gestation and was driven primarily by reduced conceptus weight. Maternal organ analysis revealed selective hepatic enlargement with apparent lipid accumulation in MNR dams near-term. Overall, these findings help to reframe nutrition-related FGR as a condition in which maternal adaptive stress responses, reduced nutritional components and placental insufficiency are mechanistically intertwined, with important implications for the design of effective interventions beyond simply nutrient supplementation.

physiology↗

bioRxiv2026

Radiotherapy Reshapes the 3D Genome in Medulloblastoma Cells

Radiotherapy is central to medulloblastoma treatment, yet the molecular and three-dimensional (3D) genome responses to irradiation remain poorly understood. Here, we integrated RNA sequencing, proteomics, and Micro-C to characterise the response of ONS-76 medulloblastoma cells to clinically relevant radiation exposures. A single 2 Gy dose induced widespread transcriptional and proteomic changes, including altered cell adhesion, migration, DNA replication, and ribosome biogenesis pathways. Integrated analysis identified LAMB3 and AKR1B10 as candidate mediators of radioresponse that remained elevated following fractionated irradiation. Micro-C profiling following single and repeated 2 Gy exposures revealed radiation-induced 3D genome remodelling. While global genome organisation remained largely stable, irradiation promoted shifts towards active A compartments, new TAD boundary formation, and transient boundary strengthening. Together, these findings provide the first genome-wide characterisation of radiation-induced 3D chromatin reorganisation in a medulloblastoma model and identify molecular and structural features associated with radioresponse.

cancer biology↗

bioRxiv2026

LNP-mediated BCL11A Editing Corrects Sickling Phenotypes and Preserves HSPC Fitness Compared to Electroporation

Hemoglobinopathies, including sickle cell disease (SCD) and thalassemia syndromes, affect millions of individuals worldwide who have limited access to curative therapies. Autologous hematopoietic stem cell transplant following ex vivo CRISPR editing of the BCL11A erythroid enhancer reactivates fetal hemoglobin (HbF) and achieves an effective cure, but the resource constraints of clinically approved procedures for editing by electroporation (EP) severely limit widespread implementation. We directly compared the functional outcomes of EP delivery of Cas9 ribonucleoprotein with lipid nanoparticle (LNP) delivery of Cas9 mRNA in primary human HSPCs obtained from healthy HbAA donors and from patients with SCD. While higher editing rates are achieved with EP, LNP-treated HSPCs exhibited greater viability and cell yields that persisted throughout a multi-stage in vitro erythroid differentiation protocol. By day 20, the yield of mature red blood cells (CD71lowCD235ahigh) was lowest in the EP cohorts. Across treatment groups, we observed HbF induction proportional to indel frequency. LNP editing of SCD patient-derived HSPCs as low as 25% modified alleles still caused HbF production and reduced the propensity for sickling of in vitro differentiated RBCs. These findings highlight the critical trade-offs among manufacturing ease, delivery-associated toxicity, and functional performance across two modalities of therapeutic genome editing for hemoglobinopathies.

bioengineering↗

bioRxiv2026

AI semantics for biomedical data integration

Researchers increasingly need to explore hypotheses that span multimodal data across different scales, organisms, and domains. In practice, this requires connecting knowledge across fragmented databases with incompatible APIs and heterogeneous annotation practices. Large language model (LLM) agents can automate this data integration process, but grounding LLM agent outputs in scientifically correct sources of truth remains a significant challenge. Here we describe our deployment of a novel AI semantics workflow using LLM agents to enable scalable data integration, grounded in biological knowledge in the form of ontologies. Our workflow comprises (1) a multi-agent system curating scientific knowledge across ontologies using the Ontology Lookup Service (OLS) as grounding; (2) an LLM embedding service to enable interoperability between scientific databases by mapping ontology terms; and (3) GrEBI, a knowledge graph and Model Context Protocol (MCP) server enabling LLM agents to conduct cross-cutting, multi-omic biomedical queries.

bioinformatics↗

bioRxiv2026

RubiSpec-MS: Determination of Rubisco CO 2 /O 2 Specificity Factor using Liquid Chromatography-Mass Spectrometry

O_LIThe specificity factor(SC/O) of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is a key kinetic parameter quantifying the ratio of carboxylation to oxygenation reactions. Current methods to measure SC/O are expensive, labor-intensive, require specialized expertise, and/or rely on radiolabeled compounds, hindering Rubisco research. C_LIO_LIWe present RubiSpec-MS (Rubisco Specificity by LC-MS/MS), a method to determine the SC/O of purified Rubiscos using liquid chromatography-coupled mass spectrometry (LC-MS/MS) for separation and sensitive detection of non-radioactive reaction products. C_LIO_LIWe benchmark RubiSpec-MS using multiple model Rubisco enzymes. We find that the assay accurately reproduces corresponding literature values for each enzyme and performs similarly in a side-by-side comparison using an established radiometric method. C_LIO_LIRubiSpec-MS provides a faster, more accessible, and highly parallelizable method to measure Rubisco SC/O using equipment common in academic core facilities and industrial laboratories. C_LI

Plant Biology↗

bioRxiv2026

Potential virulence factors in Pyrenophora teres through label-free cellular proteomics analysis

Pyrenophora teres f. teres (Ptt) is the causative agent of net blotch diseases in barley and an economically important pathogen in the barley industry worldwide. To date, however, little is known about the protein expression profile of Ptt, which is important to understand the pathogen behaviour. In this study we report the first cellular proteomics analysis of Ptt. Label-free proteomics was used to quantify the protein expression levels of two parental and one of its progeny isolates from a Ptt cross, grown in culture. One parental isolate of the cross was virulent on the barley variety Prior while the other isolate was avirulent. The progeny isolate used in this study was also virulent on Prior. A total of 3,502 proteins were identified in samples of the three Ptt isolates, of which 99 were found only in the pathogenic isolates, while another 255 proteins were significantly more abundant in the pathogenic isolates compared to the non-pathogenic isolate. Gene ontology analyses of the significant proteins revealed that the proteins increased in pathogenic isolates were involved in fatty acid elongation, biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism, nucleocytoplasmic transport, amino sugar and nucleotide sugar metabolism and metabolic pathways. These protein profiles and the bioinformatic analysis provide new biological information that can be utilised to better understand the pathogenicity of Ptt.

plant biology↗

bioRxiv2026

QTL mapping and proteomic profiling of barley: insights into resistance and susceptibility to Pyrenophora teres f. teres

Pyrenophora teres f. teres (Ptt), the causal agent of net form net blotch disease in barley, is an economically important fungal pathogen worldwide. Understanding both host resistance mechanisms and pathogen virulence factors is essential for developing durable net form net blotch resistant barley cultivars. Quantitative trait loci (QTL) mapping was conducted using a cross between two Ptt isolates, one virulent on the barley cultivar Prior and the other being avirulent. A major QTL associated with virulence on Prior was detected on chromosome 5. A progeny isolate possessing this QTL, together with the two parental isolates, was subsequently used in the proteomic analyses. Label-free proteomics was used to quantify in planta the protein profile changes in Prior following inoculations with the virulent and avirulent parental Ptt isolates, and the virulent progeny isolate. Leaf samples were collected at two (D2) and five (D5) days post-inoculation, and proteomic analyses performed to identify proteins associated with host resistance and pathogen virulence. A dataset comprising 2,886 barley proteins and 51 Ptt proteins was analysed. Principal component analysis (PCA) of the barley Prior proteomes revealed distinct clustering based on resistance and susceptibility at D5, while D2 samples formed a separate cluster. The PCA of the Ptt proteomes identified separate clusters, one comprised of the D2 and D5 avirulent parental isolate and another cluster of the virulent isolates at D5 only. Gene ontology analysis of the Prior proteins that were significantly increased in the resistant compared to the susceptible groups revealed functional categories related to protein translation, biosynthesis and chloroplast activities. The proteins that were significantly increased in the susceptible compared to the resistant Prior group were associated with organic acid and carbohydrate metabolism. The proteomic profiles and bioinformatic analysis generated in our study provide novel insights into the molecular basis of resistance and virulence in the barley-P. teres pathosystem. Key messageThis study reveals the first in planta proteomic profiles of both barley and Pyrenophora teres f. teres, identifying unique virulence-associated proteins and host responses linked to resistance and susceptibility.

plant biology↗

bioRxiv2026

Developing Potent and Selective TBK1 Molecular Glue Degraders for Cancer Immunotherapy

Immune checkpoint blockade (ICB) has transformed cancer therapy across multiple tumour types, yet primary and acquired resistance remain major barriers to durable benefit. TANK-binding kinase 1 (TBK1) has emerged as an attractive target to enhance anti-tumour immunity, acting as a serine/threonine kinase that restrains immunogenic cell death and downstream immune activation. Here we report the discovery of a first-in-class TBK1 molecular glue degrader (MGD), CCT412020, identified through high-throughput proteomics screening of a next-generation molecular glue library. CCT412020 induces rapid, potent and selective TBK1 degradation across a panel of breast cancer cell lines. A cryo-EM structure of CCT412020 in complex with CRBN/{Delta}BPB-DDB1 and TBK1-homodimer reveals an unexpected binding mode that bypasses the canonical G-loop and instead engages an unconventional site at the TBK1 homodimer interface. Functionally, TBK1 loss via CCT412020 sensitises tumour cells to TNF- and interferon-driven responses and reduced viability across a broad range of cancer cell lines. Together, these findings establish CCT412020 as a mechanistically distinct TBK1 degrader and provide a framework for developing TBK1-targeted degraders as immunomodulatory anti-cancer agents to overcome ICB resistance.

cancer biology↗

bioRxiv2026

Granulocyte colony-stimulating factor acts through calcium-permeable AMPA receptors to potentiate cocaine reward

Neuroimmune interactions have emerged as critical modulators of substance use disorders and may represent promising translational therapeutic targets. In prior work, we demonstrated that the cytokine granulocyte colony stimulating factor (G-CSF) is elevated in mice following cocaine exposure, with circulating levels correlating with cocaine intake and locomotor sensitization. Additionally, exogenous G-CSF enhances cocaine reward and increases low-dose cocaine self-administration. We have further shown that repeated G-CSF administration alters expression of glutamatergic synapse-associated proteins following cocaine-seeking behavior. Building on these findings, the present studies examined the molecular consequences of repeated administration of G-CSF, cocaine, or their combination, with a focus on glutamatergic signaling pathways. We also tested whether altered glutamate receptor expression contributes to G-CSF-mediated enhancement of cocaine reward. Repeated combined administration of G-CSF and cocaine produced robust changes in glutamate-associated and synapse-related protein expression within the nucleus accumbens and medial prefrontal cortex. These molecular adaptations were accompanied by increased synaptic density in the nucleus accumbens. Finally, pharmacological inhibition of calcium-permeable AMPA receptors within the nucleus accumbens reversed the G-CSF-induced enhancement of cocaine conditioned place preference. Together, these findings indicate that G-CSF enhances cocaine reward at least in part by promoting glutamatergic synaptic remodeling in the nucleus accumbens, identifying a neuroimmune-glutamate mechanism that may be leveraged for therapeutic intervention.

neuroscience↗

bioRxiv2025

Mosquito Viromes in England and Wales Reveal Hidden Arbovirus Signals and Limited Ecological Structuring

Outbreaks of mosquito-borne viruses are increasing in temperate regions, with West Nile and Usutu viruses now established in wide regions across Europe, and both detected in the UK. Current surveillance strategies focus on targeted approaches which are well suited for monitoring established threats but limited in their ability to detect recently described or neglected viruses. High throughput sequencing (HTS) provides an unbiased alternative, allowing simultaneous identification of well-recognised and overlooked arboviruses, alongside insect-specific viruses (ISVs) that may modulate vector competence of the insects transmitting these pathogens. This study presents the first comprehensive virome survey of Culex mosquitoes in the UK, analysing populations collected from 93 sites across England and Wales through HTS and a systematic virus discovery pipeline. Across these sites, 41 distinct viral taxa were identified, including 11 novel species. Most viruses were rare or confined to a few sites, with only three detected in more than one third of sites, suggesting the absence of a broad conserved virome across populations. Within this diversity, three arbovirus-related lineages were detected: Hedwig virus (Peribunyaviridae), Umatilla virus (Sedoreoviridae), and Atherstone virus (Peribunyaviridae), the former two representing the first detections in the UK. These putative arboviruses were embedded in viral communities that showed minimal structuring by coarse land type but a modest decline in richness with latitude across rural sites, consistent with diversity gradients observed in other microbial systems. Together, these findings provide the first national-scale baseline of Culex mosquito-associated viral diversity in the UK, and demonstrate the value of metagenomic approaches in arbovirus preparedness.

microbiology↗

bioRxiv2025

International Mouse Phenotyping Consortium: Investigating gene function and providing insights into human disease.

The International Mouse Phenotyping Consortium (IMPC; https://www.mousephenotype.org/) web portal contains phenotype data for mouse protein-coding genes derived from analysis of data obtained in a systematic and high-throughput fashion from knock-out lines produced by IMPC. The project has produced >1,400 mouse models of human disease that recapitulate phenotypes observed in patients. Over 8000 papers rely on data or reagents generated by IMPC, demonstrating the impact of the project on the research and clinical communities, and IMPC data is incorporated into other resources, such as MGI, Open Targets and UniProt. Data release (DR23.0, 2025) contains > 100 million data points from 9,277 genes and identified 113,803 significant phenotypes. To manage efficient access to this quantity of high dimensional data the IMPC web portal has been rebuilt using a cloud native architecture. The modern user interface retains the look and feel of the original portal with improvements identified through a usability study. New data visualisation and training materials for large scale data access through the API have also been developed to make the resource easier to use. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=79 SRC="FIGDIR/small/681205v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@199243borg.highwire.dtl.DTLVardef@119c12forg.highwire.dtl.DTLVardef@1da1a27org.highwire.dtl.DTLVardef@1eb141d_HPS_FORMAT_FIGEXP M_FIG C_FIG

genetics↗

bioRxiv2025

Identification of Expressed Endogenous Retroviral Element Associated Long Terminal Repeats in Devil Facial Tumour Cells

The Tasmanian devil (Sarcophilus harrisii) population has undergone a major decline in the wild due to the epidemics of two transmissible cancers known as devil facial tumours (DFT1 and DFT2). A multipronged conservation strategy is in place, but a vaccine that prevents devils from developing devil facial tumour disease would be a major step towards recovering the wild devil population. Critical to an effective DFT vaccine are target antigens. Putative non-coding regions of genomes have been identified as potential tumour-specific antigens for human cancer. These non-coding regions include long terminal repeats of endogenous retroviral elements. We identified 11,193 ERV LTR transcripts that were expressed in DFT1 or DFT2 transcriptomes but not in healthy tissue samples. Using a proteogenomic approach, we identified 33 ERV LTR peptides unique to DFT1 and/or DFT2 immunopeptidomes; four of these were validated in subsequent screens with synthetic peptides. Our study shows the potential for ERV LTRs as novel vaccine targets against DFT1 and DFT2. This method can be applied to other species for the development of cancer vaccine targets that may be shared across tumour types. summaryERV LTRs are present in the Tasmanian devil genome and devil facial tumour cell transcriptomes and immunopeptidome.

cancer biology↗

bioRxiv2025

HIV Env trimers elicit NHP apex cross-neutralizing antibodies mimicking human bNAbs

As a chronically replicating virus, HIV has evolved extreme sequence variability and effective shielding of functionally constrained spike protein determinants by host-derived glycans. Broadly neutralizing antibodies (bNAbs), though rare, can be isolated from people living with HIV, revealing conserved Env sites as key targets for vaccine development. One such target is the apex of the envelope glycoprotein (Env) spike. Here, we identified a vaccination strategy using heterologous HIV Env trimers covalently coupled to liposomes for multivalent display that resulted in the elicitation of cross-neutralizing HIV serum antibody responses in all immunized non-human primates (NHPs). Critically, we isolated a set of monoclonal antibodies (mAbs) that cross-neutralized multiple divergent HIV clinical isolates. High-resolution cryoEM structural analysis of mAbs from three different NHPs demonstrated that they targeted the Env trimer apex in a manner remarkably similar to that of the human infection-elicited, apex-directed bNAb PG9, representing a substantial advance in HIV vaccine development.

immunology↗

bioRxiv2025

Cortical-layer EEG-fMRI at 7T: experimental setup and analysis pipeline to elucidate generating mechanisms of alpha oscillations

Alpha band (8-13Hz) electroencephalography (EEG) oscillations play a key role in cognition, but their generating mechanisms are still poorly understood. Most studies investigating laminar origins of alpha oscillations have been conducted on animals using invasive intracranial recordings. To relate these findings to human alpha generation, non-invasive techniques need to be developed. Layer functional Magnetic Resonance Imaging (fMRI) at ultra-high field (UHF, 7T) allows for the interrogation of brain responses across cortical depths and combined with simultaneous EEG, provides the opportunity to gain new insight into human alpha generation mechanisms. This work establishes a framework to study the generating mechanisms of electrophysiological signals non-invasively in humans using simultaneous EEG layer-fMRI. Data were acquired on 10 participants during an eyes closed/eyes open paradigm. We showed that in 9/10 participants the quality of EEG and Blood Oxygenation Level Dependent (BOLD) fMRI data were sufficient to observe a significant negative correlation between EEG alpha power and the BOLD signal in visual cortex grey matter to the eyes open/eyes closed task. "Deveining" was performed to overcome the increase in BOLD signal toward the pial surface due to draining veins, and the effects of each of the steps in the deveining analysis on the cortical depth profiles of the negative alpha-BOLD correlations studied. The largest effect was dependent on the exclusion of voxels in the tissue immediately surrounding veins. Following deveining, the cortical depth profiles showed the negative alpha-BOLD correlations were significantly weaker in the middle depths compared with deep and superficial depths. When a boxcar rather than EEG alpha power was used to model the task, this depth-dependence was not seen, suggesting this was specific to spontaneous alpha-power modulations. In conclusion, we have established a method to non-invasively interrogate the origins of electrophysiological signals. Our alpha-BOLD depth profiles suggest the alpha signal to an eyes open-closed task is generated in superficial and deep layers suggesting top-down processes.

neuroscience↗

bioRxiv2025

Understanding the Causal Impact of Elevated Maternal Stress During Pregnancy: A Systematic Literature Review of Guinea Pig Models

Increased maternal stress during pregnancy has been linked to numerous adverse pregnancy outcomes, including preterm birth and impaired fetal development. While clinical studies have established strong associations between maternal stress and adverse pregnancy outcomes, understanding the biological mechanisms is crucial for developing effective preventive intervention. Rodent models have provided valuable insights, however physiological differences from humans limit translational relevance. This systematic review evaluated and synthesized experimental models of increased maternal stress during pregnancy in guinea pigs. Guinea pigs share key pregnancy characteristics with humans, including relevant placental structure, maternal hormonal recognition of pregnancy and precocial offspring development. We identified 43 studies using various experimental approaches categorized into three main types: behavioral models, drug/substance exposure models, and physiological challenge models. These studies demonstrated significant fetal and offspring effects, particularly sex-specific neurodevelopmental outcomes. However, maternal physiological adaptations were often superficially characterized, focusing primarily on weight gain and occasional stress hormone measurements. Most studies began interventions during established pregnancy, potentially missing critical pre-pregnancy and early pregnancy periods. Overall, this review highlights the need for future studies to consider pre-conception interventions to better model human conditions and more comprehensively examine maternal adaptations.

physiology↗

bioRxiv2025

Single-cell transcriptomics showed that maternal PCB exposure dysregulated ER stress-mediated cell type-specific responses in the liver of female offspring

Polychlorinated biphenyls (PCBs) are persistent environmental toxicants that bioaccumulate in the food chain and readily cross the placenta, raising concerns for developmental toxicity. While PCB exposure has been associated with metabolic and neurodevelopmental disorders, its cell type-specific effects on liver development remain poorly understood. This study aimed to investigate how maternal exposure to an environmentally relevant Fox River PCB mixture affects liver development in female offspring at single-cell resolution. We hypothesized that early-life PCB exposure disrupts hepatic metabolic and immune function in a cell type-specific manner. Using single-cell RNA sequencing (scRNA-seq) on liver tissue from postnatal day 28 female mice perinatally exposed to PCBs, we identified major hepatic and immune cell populations and assessed cell-specific transcriptional responses. PCB exposure significantly altered the proportions of endothelial cells and Kupffer cells and reduced neutrophil abundance. Transcriptomic analysis revealed that PCBs dysregulated key pathways in hepatocytes and non-parenchymal cells, including ER stress responses, drug metabolism, and glucose/insulin signaling. Notably, hepatocytes exhibited upregulation of phase-I drug-metabolizing enzymes and uptake transporters, but downregulation of phase-II enzymes and efflux transporters. Kupffer cells and endothelial cells had altered immune and metabolic gene expression, and intercellular communication analysis predicted disrupted fibronectin, collagen, and chemokine signaling due to PCB exposure. RT-qPCR validation confirmed increased hepatic ER stress marker expression. Together these findings demonstrate that perinatal PCB exposure induces persistent, cell type-specific transcriptomic reprogramming in the liver, impairing metabolic and immune functions. This study highlights the utility of single-cell transcriptomics for revealing toxicant effects with cellular precision during critical windows of development.

systems biology↗

bioRxiv2025

Aberrant placental structure is corrected with repeated nanoparticle-mediated IGF1 treatments in a guinea pig model of fetal growth restriction

Fetal growth restriction (FGR) is most commonly due to placental insufficiency. There are currently no treatments for placental insufficiency or FGR, and the only intervention is iatrogenic pre-term delivery. We have previously shown efficacy of repeated placental nanoparticle-mediated insulin-like 1 growth factor (IGF1) treatment in improving placental efficiency (increased fetal-placental weight ratio) and correcting fetal growth in a maternal nutrient restriction (MNR) guinea pig model of FGR. Here we investigate the structural remodeling of the placenta following 3 repeated intraplacental injections of nanoparticle-mediated hIGF1 that may underpin the published improvements in placental efficiency and fetal growth. We hypothesize placenta structural changes (reduced exchange area, altered vascular structure) that we and others have previously shown in the FGR/MNR placenta which lead to deficits in placental function are mitigated by our repeated nanoparticle-mediated hIGF1 treatment. Sham-treated MNR placentas displayed disorganized microvasculature labyrinthine exchange areas with a reduction in placental capillary number and maternal blood space areas, and an increase in the volume of the placenta macrovasculature. Repeated nanoparticle-mediated hIGF1 treatment, however, resulted in an improved exchange area with normalized placental capillary number and maternal blood space area, and macrovasculature volume. This data demonstrates repeated nanoparticle-mediated hIGF1 delivery corrects aberrant placenta structure likely leading to improved gas exchange and transfer of nutrients to the fetus restoring fetal growth.

developmental biology↗

bioRxiv2025

Establishing Comprehensive Transthoracic Echocardiography Reference Ranges for Mouse Models: Insights into the Impact of Anesthesia, Sex, and Age

Mouse models play a critical role in cardiology research, offering valuable insights into the molecular mechanisms, genetics, and potential treatments for cardiovascular diseases. However, the ability to transfer findings in mice between studies is limited by the absence of standardized protocols and valid reference values for the assessment of normal cardiac function in mice. This study aims to establish comprehensive transthoracic echocardiography (TTE) reference ranges for mice, particularly focusing on C57BL/6N wildtype controls. The study, which includes data from over 15,000 mice through the International Mouse Phenotyping Consortium (IMPC), highlights how variables such as sex, age, body weight, and anesthesia affect TTE parameters. The findings showed that anesthesia is the primary predictor of variability in cardiac function. Isoflurane and tribromoethanol anesthetized mice presented with modified cardiac function compared to conscious mice. Additionally, we observed minimal sex differences in cardiac morphology and function, except for small variations influenced by anesthesia. The effects of aging on cardiac function were modest, characterized by a decrease in heart rate and subtle changes in ventricular dimensions without evidence of pathological remodeling, likely attributable to disease-free cardiovascular aging. Validation of the reference ranges across multiple mouse strains showed that these values provide a reliable baseline for experiments involving cardiac function in mice. The data underscore the importance of using anesthesia-specific reference values when interpreting TTE results, ensuring robust comparisons in genetic and pharmacological studies. These reference ranges serve as quality assurance tools for future cardiac studies in mice, offering insights into typical TTE parameter values, supporting the detection of experimental perturbations, and contributing to more effective translation of findings from mouse to human.

genetics↗