Disease Models & Mechanisms最新文献

Reduced growth and biofilm formation at high temperatures contribute to Cryptococcus deneoformans dermatotropism. 在高温下减少生长和生物膜的形成有助于变形隐球菌的皮肤偏向性。

IF 4 3区医学

Disease Models & Mechanisms Pub Date : 2025-09-01 Epub Date: 2025-03-25 DOI: 10.1242/dmm.052141

Claudia L Charles-Niño, Gunjan M Desai, Nicholas Koroneos, Mohamed F Hamed, Neena Jain, William Lopes, Anthony Braswell, Alexander Linares, Melissa E Munzen, Joshua D Nosanchuk, Marilene H Vainstein, Luis R Martinez

{"title":"Reduced growth and biofilm formation at high temperatures contribute to Cryptococcus deneoformans dermatotropism.","authors":"Claudia L Charles-Niño, Gunjan M Desai, Nicholas Koroneos, Mohamed F Hamed, Neena Jain, William Lopes, Anthony Braswell, Alexander Linares, Melissa E Munzen, Joshua D Nosanchuk, Marilene H Vainstein, Luis R Martinez","doi":"10.1242/dmm.052141","DOIUrl":"10.1242/dmm.052141","url":null,"abstract":"Cryptococcus deneoformans (Cd) and C. neoformans (Cn) differ in geographic prevalence and dermatotropism, with Cd strains more commonly isolated from temperate regions and skin infections. Rising global temperatures prompt concerns regarding selection for environmental fungal species with increased thermotolerance, as high mammalian temperatures provide protection against many fungal species. Cd and Cn strains exhibit variations in thermal susceptibility, with Cd strains being more susceptible to higher temperatures. Here, we identified differences in capsular polysaccharide release, adhesion and biofilm formation between strains both in vivo and in vitro. Histological results suggested that the dermatotropic predilection associated with Cd relates to biofilm formation, possibly facilitating latency and extending fungal survival through protection from high temperatures. We demonstrated that Cn strains were more tolerant to mammalian and febrile temperatures than Cd strains. Similarly, Cd strains showed reduced expression of heat-shock protein 60 and 70, after prolonged exposure to high temperature. Our findings suggest that fungal adhesion, biofilm formation, inflammation and thermotolerance contribute to tissue tropism and disease manifestation by Cn and Cd, supporting the recently assigned species distinction to each of these serotypes.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correlative 3D imaging method for analysing lesion architecture in susceptible mice infected with Mycobacterium tuberculosis. 相关三维成像方法分析易感小鼠结核分枝杆菌病变结构。

IF 4 3区医学

Disease Models & Mechanisms Pub Date : 2025-09-01 Epub Date: 2025-03-26 DOI: 10.1242/dmm.052185

Caroline G G Beltran, Jurgen Kriel, Stefan M Botha, Margaret B Nolan, Alessandro Ciccarelli, Ben Loos, Maximiliano G Gutierrez, Gerhard Walzl

{"title":"Correlative 3D imaging method for analysing lesion architecture in susceptible mice infected with Mycobacterium tuberculosis.","authors":"Caroline G G Beltran, Jurgen Kriel, Stefan M Botha, Margaret B Nolan, Alessandro Ciccarelli, Ben Loos, Maximiliano G Gutierrez, Gerhard Walzl","doi":"10.1242/dmm.052185","DOIUrl":"10.1242/dmm.052185","url":null,"abstract":"Tuberculosis (TB) is characterized by the formation of heterogeneous, immune-rich granulomas in the lungs. Host and pathogen factors contribute to this heterogeneity, but the molecular and cellular drivers of granuloma diversity remain inadequately understood owing to limitations in experimental techniques. In this study, we developed an approach that combines passive CLARITY (PACT)-based clearing with light-sheet fluorescence microscopy to visualize lesion architecture and lung involvement in Mycobacterium tuberculosis-infected C3HeB/FeJ mice. Three-dimensional rendering of post-mortem lungs revealed critical architectural features in lesion development that traditional thin-section imaging could not detect. Wild-type M. tuberculosis infection resulted in organized granulomas, with median sizes increasing to 3.74×108 µm3 and occupying ∼10% of the total lung volume by day 70 post-infection. In contrast, infection with the avirulent ESX-1 deletion mutant strain resulted in diffuse and sparsely organized CD11b recruitment (median size of 8.22×107 µm3), primarily located in the lung periphery and minimally involving the airways (0.23% of the total lung space). Additionally, we present a method for volumetric correlative light and electron microscopy, enabling tracking of individual immune cell populations within granulomas.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"18 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972079/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Translating animal models of SARS-CoV-2 infection to vascular, neurological and gastrointestinal manifestations of COVID-19. 将SARS-CoV-2感染动物模型转化为COVID-19的血管、神经和胃肠道表现。

IF 4 3区医学

Disease Models & Mechanisms Pub Date : 2025-09-01 Epub Date: 2025-04-08 DOI: 10.1242/dmm.052086

James Chung, Julia Pierce, Craig Franklin, Rachel M Olson, Alan R Morrison, James Amos-Landgraf

{"title":"Translating animal models of SARS-CoV-2 infection to vascular, neurological and gastrointestinal manifestations of COVID-19.","authors":"James Chung, Julia Pierce, Craig Franklin, Rachel M Olson, Alan R Morrison, James Amos-Landgraf","doi":"10.1242/dmm.052086","DOIUrl":"10.1242/dmm.052086","url":null,"abstract":"Since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) initiated a global pandemic resulting in an estimated 775 million infections with over 7 million deaths, it has become evident that COVID-19 is not solely a pulmonary disease. Emerging evidence has shown that, in a subset of patients, certain symptoms - including chest pain, stroke, anosmia, dysgeusia, diarrhea and abdominal pain - all indicate a role of vascular, neurological and gastrointestinal (GI) pathology in the disease process. Many of these disease processes persist long after the acute disease has been resolved, resulting in 'long COVID' or post-acute sequelae of COVID-19 (PASC). The molecular mechanisms underlying the acute and systemic conditions associated with COVID-19 remain incompletely defined. Appropriate animal models provide a method of understanding underlying disease mechanisms at the system level through the study of disease progression, tissue pathology, immune system response to the pathogen and behavioral responses. However, very few studies have addressed PASC and whether existing models hold promise for studying this challenging problem. Here, we review the current literature on cardiovascular, neurological and GI pathobiology caused by COVID-19 in patients, along with established animal models of the acute disease manifestations and their prospects for use in PASC studies. Our aim is to provide guidance for the selection of appropriate models in order to recapitulate certain aspects of the disease to enhance the translatability of mechanistic studies.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"18 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143802718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Translational lessons from the balanced immune system in bats. 蝙蝠平衡免疫系统的翻译经验。

IF 4 3区医学

Disease Models & Mechanisms Pub Date : 2025-09-01 Epub Date: 2025-02-19 DOI: 10.1242/dmm.050763

Wei Lun Ng, Lin-Fa Wang

引用次数: 0

The inflammasome adaptor pycard is essential for immunity against Mycobacterium marinum infection in adult zebrafish. 炎性小体接头pycard对成年斑马鱼对海洋分枝杆菌感染的免疫至关重要。

IF 4 3区医学

Disease Models & Mechanisms Pub Date : 2025-09-01 Epub Date: 2025-03-24 DOI: 10.1242/dmm.052061

Meri Uusi-Mäkelä, Sanna-Kaisa Emilia Harjula, Maiju Junno, Alina Sillanpää, Reetta Nätkin, Mirja Tellervo Niskanen, Anni Karoliina Saralahti, Matti Nykter, Mika Rämet

{"title":"The inflammasome adaptor pycard is essential for immunity against Mycobacterium marinum infection in adult zebrafish.","authors":"Meri Uusi-Mäkelä, Sanna-Kaisa Emilia Harjula, Maiju Junno, Alina Sillanpää, Reetta Nätkin, Mirja Tellervo Niskanen, Anni Karoliina Saralahti, Matti Nykter, Mika Rämet","doi":"10.1242/dmm.052061","DOIUrl":"10.1242/dmm.052061","url":null,"abstract":"Inflammasomes regulate the host response to intracellular pathogens including mycobacteria. We have previously shown that the course of Mycobacterium marinum infection in adult zebrafish (Danio rerio) mimics the course of tuberculosis in human. To investigate the role of the inflammasome adaptor pycard in zebrafish M. marinum infection, we produced two zebrafish knockout mutant lines for the pycard gene with CRISPR/Cas9 mutagenesis. Although the zebrafish larvae lacking pycard developed normally and had unaltered resistance against M. marinum, the loss of pycard led to impaired survival and increased bacterial burden in the adult zebrafish. Based on histology, immune cell aggregates, granulomas, were larger in pycard-deficient fish than in wild-type controls. Transcriptome analysis with RNA sequencing of a zebrafish haematopoietic tissue, kidney, suggested a role for pycard in neutrophil-mediated defence, haematopoiesis and myelopoiesis during infection. Transcriptome analysis of fluorescently labelled, pycard-deficient kidney neutrophils identified genes that are associated with compromised resistance, supporting the importance of pycard for neutrophil-mediated immunity against M. marinum. Our results indicate that pycard is essential for resistance against mycobacteria in adult zebrafish.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Patient advocacy in tuberculosis research and treatment: an interview with Zolelwa Sifumba. 结核病研究和治疗中的患者倡导：对Zolelwa Sifumba的采访。

IF 4 3区医学

Disease Models & Mechanisms Pub Date : 2025-09-01 Epub Date: 2025-03-19 DOI: 10.1242/dmm.052316

Zolelwa Sifumba

引用次数: 0

A homozygous human WNT11 variant is associated with laterality, heart and renal defects. 纯合子人类WNT11变异与偏侧、心脏和肾脏缺陷有关。

IF 4 3区医学

Disease Models & Mechanisms Pub Date : 2025-04-09 DOI: 10.1242/dmm.052211

Henrike Berns, Damian Weber, Maximilian Haas, Zeineb Bakey, Magdalena Maria Brislinger-Engelhardt, Miriam Schmidts, Peter Walentek

{"title":"A homozygous human WNT11 variant is associated with laterality, heart and renal defects.","authors":"Henrike Berns, Damian Weber, Maximilian Haas, Zeineb Bakey, Magdalena Maria Brislinger-Engelhardt, Miriam Schmidts, Peter Walentek","doi":"10.1242/dmm.052211","DOIUrl":"https://doi.org/10.1242/dmm.052211","url":null,"abstract":"Wnt signaling plays important roles during vertebrate development, including left-right axis specification as well as heart and kidney organogenesis. We identified a homozygous human WNT11 variant in an infant with Situs inversus totalis, complex heart defects and renal hypodysplasia, and we used Xenopus embryos to functionally characterize this variant. WNT11c.814delG encodes a protein with reduced stability that lost signaling activity in vivo. This is remarkable, because the variant encodes a truncated ligand with nearly identical length and predicted structure to dominant-negative Wnts. Furthermore, we demonstrate that alteration of the truncated C-terminal end can restore stability and signaling activity similar to Xenopus dominant-negative Wnt11b. Our study also suggests similar functions for WNT11 in human development as described in model organisms. Therefore, biallelic WNT11 dysfunction should be considered as novel genetic cause in syndromal human phenotypes presenting with congenital heart defects and renal hypoplasia, with or without laterality defects. The work presented here enhances our understanding of human development and structure-function relationships in Wnt ligands.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identifying novel links between cardiovascular disease and insomnia by Drosophila modeling of genes from a pleiotropic GWAS locus. 通过多效性GWAS基因的果蝇模型确定心血管疾病和失眠之间的新联系。

IF 4 3区医学

Disease Models & Mechanisms Pub Date : 2025-04-03 DOI: 10.1242/dmm.052139

Farah Abou Daya, Torrey Mandigo, Lily Ober, Dev Patel, Matthew Maher, Suraj Math, Cynthia Tchio, James A Walker, Richa Saxena, Girish C Melkani

{"title":"Identifying novel links between cardiovascular disease and insomnia by Drosophila modeling of genes from a pleiotropic GWAS locus.","authors":"Farah Abou Daya, Torrey Mandigo, Lily Ober, Dev Patel, Matthew Maher, Suraj Math, Cynthia Tchio, James A Walker, Richa Saxena, Girish C Melkani","doi":"10.1242/dmm.052139","DOIUrl":"https://doi.org/10.1242/dmm.052139","url":null,"abstract":"Insomnia symptoms double the risk of cardiovascular disease (CVD), yet shared genetic pathways remain unclear. Genome-wide association studies (GWAS) identified a genetic locus (near ATP5G1, UBE2Z, SNF8, IGF2BP1, and GIP) linked to insomnia and CVD. We used Drosophila models to perform tissue-specific RNAi knockdowns of four conserved orthologues (ATPSynC, Lsn, Bruce, and Imp) in neurons and the heart. Neuronal-specific knockdown of ATPSynC, Imp, and Lsn impaired sleep quantity and quality. In contrast, cardiac knockdown of ATPSynC and Lsn reduced cardiac function and lifespan, with Lsn knockdown also causing cardiac dilation and myofibrillar disorganization. Cross-tissue effects were evident: neuronal Imp knockdown compromised cardiac function, while cardiac ATPSynC and Lsn knockdown increased sleep fragmentation and inflammation (marked by Upd3 elevation in the heart or head). Overexpression of Upd3 in neurons impaired cardiac function, while its overexpression in the heart disrupted sleep. Our findings reveal conserved genes mediating tissue-specific and cross-tissue interactions between sleep and cardiac function, providing novel insights into genetic mechanisms linking insomnia and CVD through inflammation.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modeling ANKRD26 5'-UTR mutation-related thrombocytopenia in zebrafish. 模拟斑马鱼ANKRD26 5'-UTR突变相关的血小板减少症。

IF 4 3区医学

Disease Models & Mechanisms Pub Date : 2025-04-02 DOI: 10.1242/dmm.052222

Liang Zheng, Zhijian Wu, Noritaka Yada, Szumam Liu, Cindy Lin, Antonia Bignotti, Xinyang Zhao, X Long Zheng

{"title":"Modeling ANKRD26 5'-UTR mutation-related thrombocytopenia in zebrafish.","authors":"Liang Zheng, Zhijian Wu, Noritaka Yada, Szumam Liu, Cindy Lin, Antonia Bignotti, Xinyang Zhao, X Long Zheng","doi":"10.1242/dmm.052222","DOIUrl":"https://doi.org/10.1242/dmm.052222","url":null,"abstract":"Mutations in 5'-untranslated region (5'-UTR) of ANKRD26 (ankyrin repeat domain-containing protein 26) are associated with hereditary thrombocytopenia-2 (THC2). However, the causative role of these mutations and the mechanisms underlying THC2 are not fully established. Here, we report for the first time that zebrafish carrying a deletion of two nucleotides (Δ2) in the 5'-UTR of ankrd26 recapitulate some of the key laboratory features of THC2. Ankrd26ku6 (homozygous for the Δ2 deletion in the 5'-UTR) fish larvae exhibited significantly increased expression of ankrd26 mRNA and protein. Ankrd26ku6 adult fish exhibited spontaneous thrombocytopenia. Furthermore, the thrombocytes from ankrd26ku6 showed an enhanced ability to adhere and aggregate on a collagen surface under flow. Proteomic profiling demonstrated a dramatic upregulation of Ninjurin1 in young thrombocytes from ankrd26ku6 fish compared with those from wild-type controls. The ankrd26ku6 fish with a homozygous nacre allele developed myelodysplastic syndrome at old age. ANKRD26 protein levels were also significantly increased in platelets and plasma from patients with immune thrombotic thrombocytopenic purpura compared with those from healthy controls. We conclude that ANKRD26 overexpression, resulting from either hereditary or acquired mechanisms, may contribute to thrombocytopenia, thrombosis, and hematologic malignancies.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction: A novel mouse model of Duchenne muscular dystrophy carrying a multi-exonic Dmd deletion exhibits progressive muscular dystrophy and early-onset cardiomyopathy. 更正：一种携带多外显子Dmd缺失的杜氏肌营养不良小鼠模型表现出进行性肌营养不良和早发性心肌病。

IF 4 3区医学

Disease Models & Mechanisms Pub Date : 2025-04-01 Epub Date: 2025-04-04 DOI: 10.1242/dmm.052372

Tatianna Wai, Ying Wong, Abdalla Ahmed, Grace Yang, Eleonora Maino, Sydney Steiman, Elzbieta Hyatt, Parry Chan, Kyle Lindsay, Nicole Wong, Diane Golebiowski, Joel Schneider, Paul Delgado-Olguı N, Evgueni A Ivakine, Ronald D Cohn

引用次数: 0