Mammalian Genome最新文献

{"title":"Identification and validation of mitochondrial endoplasmic reticulum membrane-related genes in atherosclerosis.","authors":"Li-Rong Wang, Chun-Xi Zhang, Lv-Bo Tian, Jie Huang, Li-Jun Jia, Hao Tao, Neng-Wei Yu, Bing-Hu Li","doi":"10.1007/s00335-025-10124-0","DOIUrl":"https://doi.org/10.1007/s00335-025-10124-0","url":null,"abstract":"<p><p>The mitochondria-associated endoplasmic reticulum membrane is implicated in atherosclerosis (AS). However, its precise molecular mechanisms remain undefined. This study identified KLRC1 and SOCS2 as key protective genes against AS through transcriptomic analysis integrated with Mendelian randomization. Both genes exhibited significantly reduced expression in the AS group. Immune infiltration analysis revealed a strong positive correlation between activated CD8⁺ T cells and these genes, while eosinophils displayed the most pronounced negative correlation with KLRC1, and regulatory T cells exhibited the strongest negative association with SOCS2. Notably, SOCS2 emerged as a pivotal protective factor, offering novel insights into AS pathogenesis and providing a robust theoretical foundation for early diagnosis and potential therapeutic strategies.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mouse resource at National Resource Center for Mutant Mice of China.","authors":"Bingzhou Han, Dongshen Chen, Zhong Chen, Ting Wang, Kaiyuan Zi, Rui Feng, Xiaoliu Yang, Ling'en Li, Juan Liang, Xiang Gao","doi":"10.1007/s00335-025-10118-y","DOIUrl":"https://doi.org/10.1007/s00335-025-10118-y","url":null,"abstract":"<p><p>Mouse models serve as the most important laboratory resource for both biomedical research and preclinical study of drug development. National Resource Center of Mutant Mice (NRCMM) of China was initiated in 2001 and became one of the 31 members of National Science and Technology Resource Sharing Platform in 2019. Currently, NRCMM is co-managed by Model Animal Research Center of Nanjing University and Gempharmatech (GPT, a Shanghai Exchange enlisted public company). Dedicated to produce and collect genetic edited mouse models, NRCMM holds more than 22,000 mouse strains in 2024, compared with 18,500 strains reported in 2022. This review provides an update on our Knock-Out All Project (KOAP) and highlights resources available for immune system reconstitution models, disease models, and chromosome substitution strains at NRCMM.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The RSPO2 gene is associated with bilateral anterior amelia in Chihuahuas.","authors":"Lucie Chevallier, Marin Green, Julia Vo, Karen Vernau, Denis J Marcellin-Little, Vidhya Jagannathan, Tosso Leeb, Danika Bannasch","doi":"10.1007/s00335-025-10123-1","DOIUrl":"https://doi.org/10.1007/s00335-025-10123-1","url":null,"abstract":"<p><p>Bilateral anterior amelia (BAA) is the congenital absence of thoracic limbs and has been reported in the Chihuahua as an autosomal recessive disorder. In some cases, the digits of the pelvic limbs can be variably affected, but otherwise, the pelvic limbs are generally spared. A GWAS performed with nine BAA affected Chihuahuas identified a significant association on chromosome 13, and homozygosity mapping delineated a 2.1 Mb chromosomal region containing the RSPO2 gene. Loss of function variants of RSPO2 in humans and cattle has been associated with the absence of all limbs. Six affected Chihuahuas were whole genome sequenced (WGS) and aligned to the CanFam4 assembly. SNVs, small indels, and structural variants within the critical interval that fitted a recessive model were investigated. Three SNVs (NC_049234.1:g.8891861C > T; NC_049234.1:g.8974204C > T and NC_049234.1:g.9789424G > A) were homozygous in five cases and absent from 3,418 genetically diverse control genome sequences, except for one Small Poodle that was heterozygous. One SNV resided in RSPO2's second intron, while the two others were intergenic. The three candidate variants were genotyped in 7 additional cases and 100 control Chihuahuas. Twelve of 13 cases were homozygous for the mutant allele, and one case was heterozygous. Controls were either homozygous for the reference allele (97%) or heterozygous (3%). Our data should facilitate genetic testing of Chihuahuas to prevent the unintentional production of BAA affected dogs. Moreover, the identification of these variants enhances understanding of RSPO2 gene function in limb development.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of NETs-related genes as diagnostic biomarkers in ischemic stroke using RNA sequencing and single-cell analysis.","authors":"Rongxing Qin, Wei Xu, Qingchun Qin, Xiaojun Liang, Xinyu Lai, Minshan Xie, Li Chen","doi":"10.1007/s00335-025-10117-z","DOIUrl":"https://doi.org/10.1007/s00335-025-10117-z","url":null,"abstract":"<p><p>Neutrophil extracellular traps (NETs) are increasingly recognized for their involvement in ischemic stroke (IS), yet their precise contribution to IS outcomes is not fully understood. This study aims to elucidate the role of NETs in IS progression and identify potential biomarkers and therapeutic targets. In this study, mice were subjected to middle cerebral artery occlusion (MCAO). RNA sequencing was conducted on brain tissue samples to identify differentially expressed genes (DEGs) using the \"limma\" package. The diagnostic potential of these biomarkers was assessed using receiver operating characteristic (ROC) curve analysis. Additionally, single-cell RNA sequencing data were analyzed with the Seurat package to further investigate the cellular dynamics. We identified DEGs, and NETs-related genes associated with IS progression. Specifically, Ceacam3, Tnf, Selp, and Fcgr4 were found to be upregulated in MCAO samples, exhibiting diagnostic value as biomarkers for IS. Immune infiltration analysis indicated associations between these genes and various immune cell types. Gene Set Enrichment Analysis (GSEA) revealed their involvement in IS-related pathways, including ferroptosis, IL-17 signaling, leukocyte transendothelial migration, necroptosis, and NETs formation. Single-cell data confirmed the expression of Tnf, Selp, and Fcgr4 in neutrophils. CellChat analysis uncovered key cell-cell interactions in IS, emphasizing the role of neutrophils in communicating with microglia and T cells via the JAM pathway, with Thbs1 and Cd47 as key mediators. The findings provide insights into the cellular and molecular mechanisms underlying IS and may pave the way for novel therapeutic strategies targeting NETs in IS patients.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rat models of musculoskeletal lysosomal storage disorders and their role in pre-clinical evaluation of gene therapy approaches.","authors":"Sara Marcó, Sergio Muñoz, Fatima Bosch, Veronica Jimenez","doi":"10.1007/s00335-025-10121-3","DOIUrl":"https://doi.org/10.1007/s00335-025-10121-3","url":null,"abstract":"<p><p>Mice have been a cornerstone of biomedical research for decades for studying a wide range of biological processes, disease mechanisms, and the assessment of therapies. Moreover, mice present several practical advantages such as small size, low cost and ease of genetic manipulation. While mice offer numerous benefits, for certain disease areas, rat models provide a closer representation of human disease progression, offering better insights for translational research and therapeutic development. This closer resemblance is particularly important for research focusing on diseases involving the cardiovascular and musculoskeletal system. In rats, the pathophysiology of these diseases mirrors the clinical alterations observed in humans. This review focuses on the key phenotypic differences between mouse and rat models of lysosomal storage disorders that specifically manifest with cardiac, skeletal muscle, and bone and joint involvement (Pompe and Danon diseases, and Maroteaux-Lamy and Morquio A syndromes). Furthermore, we discuss the therapeutic potential of various adeno-associated viral vector-mediated gene therapies that have been evaluated in these rat models, highlighting their contributions to advancing treatment options for these debilitating conditions.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The power of mouse models in the diagnostic odyssey of patients with rare congenital anomalies.","authors":"Stephen R F Twigg, Nicholas D E Greene, Deborah J Henderson, Pleasantine Mill, Karen J Liu","doi":"10.1007/s00335-025-10114-2","DOIUrl":"https://doi.org/10.1007/s00335-025-10114-2","url":null,"abstract":"<p><p>Congenital anomalies are structural or functional abnormalities present at birth, which can be caused by genetic or environmental influences. The availability of genome sequencing has significantly increased our understanding of congenital anomalies, but linking variant identification to functional relevance and definitive diagnosis remains challenging. Many genes have unknown or poorly understood functions, and with a lack of clear genotype-to-phenotype correlations, it can be difficult to move from variant discovery to diagnosis. Thus, for most congenital anomalies, there still exists a \"diagnostic odyssey\" which presents a significant burden to patients, families and society. Animal models are essential in the gene discovery process because they allow researchers to validate candidate gene function and disease progression within intact organisms. However, use of advanced model systems continues to be limited due to the complexity of efficiently generating clinically relevant animals. Here we focus on the use of precisely engineered mice in variant-to-function studies for resolving molecular diagnoses and creating powerful preclinical models for congenital anomalies, covering advances in genomics, genome editing and phenotyping approaches as well as the necessity for future initiatives aligning animal modelling to deep patient multimodal datasets.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the brain-joint axis: genetic, transcriptomic, and cohort insights from neuroticism to osteoarthritis.","authors":"Jingwei Zhang, Yingjie Li, Yongzhen Li, Hongwei Liu","doi":"10.1007/s00335-025-10112-4","DOIUrl":"https://doi.org/10.1007/s00335-025-10112-4","url":null,"abstract":"<p><p>The causal relationships between neuroticism and osteoarthritis (OA) were inconclusive in observational studies. We conducted bidirectional two-sample Mendelian randomization (MR) and transcriptome-wide association studies to determine the associations and the underlying transcriptomic basis. The summary-level genome-wide association study data for any site OA, knee OA, erosive hand OA, and hip OA were mainly derived from UK Biobank, and neuroticism was derived from CTGlab. We then utilized weighted regression and propensity score matching (PSM) models to investigate the relationship between neuroticism and OA in 11,948 participants of European ancestry from the National Health and Nutrition Examination Survey from 2005 to 2018. Bidirectional two-sample MR studies revealed that feelings of being fed-up, a sense of miserableness, mood swings, and a higher neuroticism score were all linked to an increased risk of OA. These factors were specifically associated with OA at various sites, including the knee. Conversely, there was no evidence to suggest that OA had any influence on traits related to neuroticism. In a comprehensive analysis that accounted for variables such as age, sex, blood lipids, blood glucose, body weight, smoking, alcohol consumption, and physical activity, it was determined that mental fluctuation significantly increased the incidence of self-reported OA (OR 1.37, 95% CI 1.20-1.58, P < 0.001) based on weighted regression. Further confirmation was provided by PSM analysis, which showed that mental fluctuation was associated with a higher incidence of self-reported OA (OR 1.28, 95% CI 1.08-1.52, P = 0.004). Moreover, differentially expressed genes were enriched in several biological processes, including the cell cycle, lipid metabolism, RNA processing, and immuno-inflammatory responses. The results revealed significant genetic and population-based associations, as well as underlying mechanisms, between neuroticism and osteoarthritis, supporting the concept of a brain-joint axis.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the therapeutic effect of melatonin targeting common biomarkers in testicular germ cell tumor, prostate adenocarcinoma, and male infertility: an integrated biology approach.","authors":"Uddesh Ramesh Wanjari, Abilash Valsala Gopalakrishnan","doi":"10.1007/s00335-025-10119-x","DOIUrl":"10.1007/s00335-025-10119-x","url":null,"abstract":"<p><p>Globally, male infertility (MI) is a major concern. Several other comorbidities related to MI are testicular germ cell tumor (TGCT) and prostate adenocarcinoma (PRAD). This study focuses on finding the common biomarkers among these diseases and their interaction with Melatonin (MLT). The differential expressed genes were retrieved using the GEPIA2 database for TGCT and PRAD, whereas the DISGENET database for MI-related genes. InteractiVenn was performed in response to identify the common genes. The STAG3, RNF212, DDX3Y, DPY19L2, TPCN1, KLK3, GNRH1, DMD, CCDC146, and DNAH1 are found to be involved in all these diseases. The gene ontologies and pathway enrichment analysis were done for these significant genes in response to identifying and accessing the involvement of these genes in other processes. MLT is a neuroendocrine hormone with high therapeutic properties. MLT showed the best binding energy with DDX3Y among all the proteins. Molecular dynamic simulation (MDS) of MLT with DDX3Y was performed and found to be -52.382 ± 13.110 kJ/mol binding energy. The RMSD, RMSF, SASA, RG, H-bond, FEL, PCA, and MM-PBSA analysis confirm the stability and compactness of the DDX3Y-MLT complex. The MDS results indicate that MLT is a promising therapeutic option for enhancing DDX3Y expression, which will support spermatogenesis. Additionally, the hub genes were identified based on MCC parameters from the merged interactive network of common genes in response to finding significant genes that can be a potential biomarker for the diagnosis of diseases.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut metabolites and functional recovery after ischemic stroke: a genetic perspective.","authors":"Wenpeng Wu, Luwen Zhu, Jiongliang Zhang, Xinyue Li, Donghui Yu, Yuting Wang, Yumeng Su, Xiangyu Wei, Hanwen Ma, Wenjing Song, Jinting Li, Lili Teng, Qiang Tang, Minmin Wu","doi":"10.1007/s00335-025-10120-4","DOIUrl":"10.1007/s00335-025-10120-4","url":null,"abstract":"<p><p>The current study explores the relationship between genetically predicted gut metabolites and functional outcomes following ischemic stroke, utilizing the Mendelian Randomization (MR) framework. Genetic information regarding gut microbiota-derived metabolites was sourced from 2076 participants of European descent participating in the Framingham Heart Study. Data on functional outcomes 90 days post-ischemic stroke were acquired from the Genetics of Ischemic Stroke Functional Outcomes Network (n = 6,021). Genetic proxies for gut microbiota were identified from a large-scale GWAS study by the MiBioGen consortium, encompassing 18,340 samples across 24 distinct cohorts. The inverse variance weighting method served as the primary analytical approach. Host gene-influenced gut microbiota was linked to both favorable and unfavorable functional outcomes post-ischemic stroke, involving nine and two specific microbiomes, respectively. Moreover, genetically predicted metabolites of gut microbiota showed associations with functional outcomes post-ischemic stroke, exhibiting one positive and five negative correlations. Sensitivity analyses employing alternative methods and models, not adjusted for baseline stroke severity, consistently supported these findings. This research provides genetic substantiation of the influence of specific gut microbiota and metabolites on the recovery process following ischemic stroke, suggesting a potential causal relationship. This insight offers valuable perspectives on the trajectory of post-stroke recovery and prognostic development.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of EXO1 as a potential biomarker associated with prognosis and tumor immune microenvironment for specific human cancers.","authors":"Jingyun Wang, Fen Liu, Jianfu Heng, Guoli Li","doi":"10.1007/s00335-024-10092-x","DOIUrl":"10.1007/s00335-024-10092-x","url":null,"abstract":"<p><p>Exonuclease 1 (EXO1) is an evolutionarily conserved exonuclease, which have function on maintaining genomic stability. Elevated expression of EXO1 has been reported in certain cancers. However, a comprehensive pan-cancer analysis of EXO1 is still lacking and its role in human cancer development remains poorly understood. This study aims to investigate the genetic alterations and expression perturbations of EXO1 and evaluate its potential clinical relevance in different cancer types. By employing powerful bioinformatics tools and utilizing data sourced from The Cancer Genome Atlas and the Genotype-Tissue Expression datasets, a comprehensive pan-cancer analysis of EXO1 was conducted, including an examination of gene expression, alterations in genetics, DNA methylation patterns, survival outcomes, clinical traits, immune features, and functional enrichment analysis. EXO1 was found to be highly expressed across 20 tumor types, including lung adenocarcinoma, lung squamous cell carcinoma, and breast invasive carcinoma. The expression levels of EXO1 are frequently associated with later clinical stages and unfavorable outcomes. Genetic alterations in EXO1 were predominantly found to be amplified in a pan-cancer context. A total of 131 missense mutations, 24 truncation mutations, 1 in-frame mutation, 6 splice site mutations, and 1 fusion mutation were identified. Interestingly, a significant co-occurrence of alterations in EXO1 with other ten gene alterations were identified. The expression of EXO1 in multiple tumors showed a significant correlation with tumor mutational burden, microsatellite instability, and genes related to immunological checkpoints. In most types of cancer, a strong correlation exists between the expression of EXO1 and the infiltration of CD4⁺ Th2 cells, memory CD4⁺ T cells, myeloid-derived suppressor cells, and common lymphoid progenitors. Analysis of 150 genes related to EXO1 demonstrate an enrichment in processes such as cell cycle regulation, DNA damage repair, and relevant signaling pathways, suggesting a possible mechanism through which EXO1 may facilitate tumor development. This study offers a deep insight into the role of EXO1 in different types of human cancers, indicating that EXO1 could act as an important prognostic biomarker and a therapeutic target for certain types of cancer.</p>","PeriodicalId":18259,"journal":{"name":"Mammalian Genome","volume":" ","pages":"262-279"},"PeriodicalIF":2.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}