Disease Models & Mechanisms最新文献_第3页

Female-specific alterations in insulin dynamics are associated with glucose tolerance in a Glut1DS mouse model. 在Glut1DS小鼠模型中，女性特异性胰岛素动力学改变与葡萄糖耐量有关。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-09-01 Epub Date: 2026-09-21 DOI: 10.1242/dmm.052836

Tamio Furuse, Tomoko Kushida, Akiko Shinogi, Mao Ozaki, Ryoko Yanagisawa, Masaru Tamura

{"title":"Female-specific alterations in insulin dynamics are associated with glucose tolerance in a Glut1DS mouse model.","authors":"Tamio Furuse, Tomoko Kushida, Akiko Shinogi, Mao Ozaki, Ryoko Yanagisawa, Masaru Tamura","doi":"10.1242/dmm.052836","DOIUrl":"10.1242/dmm.052836","url":null,"abstract":"Glucose transporter type 1 deficiency syndrome (Glut1DS) is a rare autosomal dominant genetic disorder caused by mutations in SLC2A1, which results in impaired glucose transport across the blood-brain barrier. Patients with Glut1DS present with various symptoms, including seizures, delayed development and movement disorders. The current first-line therapy - ketogenic diet - has shown variable efficacy, highlighting the need to explore alternative therapeutic strategies. This study aimed to investigate comprehensive phenotypic characteristics of the Glut1DS mouse model B6(D2)-Slc2a1<Rgsc200>/1Rbrc to establish foundational data for identifying novel therapeutic targets. The Slc2a1Rgsc200 mutant mouse was phenotypically characterized at the Japan Mouse Clinic of the RIKEN BioResource Research Center by using a phenotyping pipeline that included intraperitoneal glucose tolerance test (IPGTT) and clinical blood chemistry analyses. Heterozygous Glut1DS mutants exhibited no differences in basal plasma glucose or glycosylated hemoglobin A1c levels when compared to wild-type controls. However, female heterozygous mutants showed decreased glucose levels during IPGTT, accompanied by increased plasma insulin levels following glucose administration. These findings support recent evidence linking insulin signaling to seizure control in patients with Glut1DS, as demonstrated in human studies.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"19 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651954/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012141","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

Cardiac magnetic resonance imaging reveals myocardial fibrosis and systolic dysfunction in mitochondrial trifunctional protein-deficient mice. 心脏MRI显示线粒体三功能蛋白缺陷小鼠心肌纤维化和收缩功能障碍。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-09-01 Epub Date: 2026-09-25 DOI: 10.1242/dmm.052921

Eduardo Vieira Neto, Shakuntala Basu, Thomas J Becker-Szurszewski, Sean Hartwick, Kristina E Schwab, Yijen Wu, Jerry Vockley

{"title":"Cardiac magnetic resonance imaging reveals myocardial fibrosis and systolic dysfunction in mitochondrial trifunctional protein-deficient mice.","authors":"Eduardo Vieira Neto, Shakuntala Basu, Thomas J Becker-Szurszewski, Sean Hartwick, Kristina E Schwab, Yijen Wu, Jerry Vockley","doi":"10.1242/dmm.052921","DOIUrl":"10.1242/dmm.052921","url":null,"abstract":"Cardiomyopathy is an important manifestation in patients with fatty acid oxidation disorders and represents a major cause of morbidity and early mortality in mitochondrial trifunctional protein (TFP) deficiency. Although a mouse model carrying the TFP β-subunit p.Met404Lys mutation (βTFP-deficient mice) has been described, cardiac involvement in this model has not been systematically characterized. Here, we combined cardiac histology and multiparametric cardiac magnetic resonance imaging (CMR) to define myocardial structure, function and tissue characteristics in this mouse model. Histological analysis with automated whole-slide collagen quantification revealed myocardial fibrosis with collagen deposition in mutant hearts, and CMR demonstrated increased myocardial extracellular volume in both male and female homozygous mutants. Homozygous males showed reduced ejection fraction, impaired systolic strain and increased left ventricular end-systolic volume, indicating systolic dysfunction. Male mice were more severely affected than females and exhibited reduced survival. Together, these findings demonstrate that βTFP-deficient mice develop fibrotic cardiomyopathy with systolic dysfunction, reproducing important cardiac features observed in human TFP deficiency. This work establishes the model as a relevant platform for investigating disease mechanisms and therapeutic strategies for cardiomyopathy in TFP deficiency.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663596","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

A bioengineered platform reveals progressive impairment of skeletal muscles by metabolic dysfunction-associated steatotic liver disease-derived factors. masld衍生因子对生物工程骨骼肌进行性损伤：肝脏诱导肌肉萎缩模型平台。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-09-01 Epub Date: 2026-09-17 DOI: 10.1242/dmm.052820

Armando Cortés-Reséndiz, Juan M Fernández-Costa, Maria Sabater-Arcís, Francesco De Chiara, Javier Ramón-Azcón

{"title":"A bioengineered platform reveals progressive impairment of skeletal muscles by metabolic dysfunction-associated steatotic liver disease-derived factors.","authors":"Armando Cortés-Reséndiz, Juan M Fernández-Costa, Maria Sabater-Arcís, Francesco De Chiara, Javier Ramón-Azcón","doi":"10.1242/dmm.052820","DOIUrl":"10.1242/dmm.052820","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD) affects >30% of the global population and is increasing in prevalence to become the most common liver disorder. MASLD can influence distal organs via secreted mediators, and up to 43% of patients show sarcopenia or related muscle-wasting phenotypes. We developed a modular human three-dimensional bioengineered liver-muscle platform to dissect causal liver-muscle crosstalk. Liver constructs recapitulated steatosis and transition to metabolic dysfunction-associated steatohepatitis (MASH), with inflammatory, apoptotic, immune cell-recruiting and pro-fibrotic signatures. Transferring liver-derived conditioned media to engineered muscles revealed severity-dependent impairment of contractile performance, altered protein balance and myogenic regulation. Contractility declined progressively from steatosis to MASH. Steatotic liver conditioned media reduced myotube size, whereas MASH conditioned media triggered a compensatory program that partially preserved size despite functional loss. Muscle exposure to MASLD mediators was associated with disrupted autophagic degradation, consistent with impaired flux and accumulation of autophagosomes and lysosomes. This scalable human platform enables systematic investigation of MASLD extrahepatic mechanisms and provides a testbed for perturbations and interventions targeting liver-driven muscle wasting.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618840","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

An antioxidant therapy elicits distinct transcriptome responses in 22q11-deleted upper layer cortical projection neurons. 抗氧化治疗在22q11缺失的上层皮质投射神经元中引起明显的转录组反应。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-09-01 Epub Date: 2026-09-09 DOI: 10.1242/dmm.052786

Shah Rukh, Daniel W Meechan, Abra Roberts, Connor Siggins, Zachary D Erwin, Thomas M Maynard, Anthony-S LaMantia

{"title":"An antioxidant therapy elicits distinct transcriptome responses in 22q11-deleted upper layer cortical projection neurons.","authors":"Shah Rukh, Daniel W Meechan, Abra Roberts, Connor Siggins, Zachary D Erwin, Thomas M Maynard, Anthony-S LaMantia","doi":"10.1242/dmm.052786","DOIUrl":"10.1242/dmm.052786","url":null,"abstract":"We characterized in vitro and in vivo responses to the antioxidant N-acetyl cysteine (NAC) in mice that model the heterozygous deletion of genes at human chromosome 22q11.2 associated with the 22q11.2 deletion syndrome (22q11DS). In this 'large deletion' (LgDel) mouse model, NAC restores the growth and connectivity of developing upper layer cortical projection neurons (L 2/3 PNs) and improves their cognitive performance. It ameliorates L 2/3 PN developmental pathology without restoring wild-type (WT) growth patterns or expression levels of downstream targets of 22q11-deleted genes. Instead, neuronal growth and antioxidant defense genes are differentially expressed when comparing LgDel and WT PNs, i.e. some are generally regulated by NAC, while others are responsive only in the context of 22q11 deletion. NAC also elicits the expression of genes involved in growth and antioxidant defense in differentiating 22q11-deleted L 2/3 PNs in postnatal LgDel mouse cortex rather than restores 22q11 downstream targets to WT levels; however, these L 2/3 PN-selective in vivo changes differ substantially from those in primary culture. Thus, the therapeutic response to NAC that diminishes oxidative stress-related L 2/3 PN developmental circuit and behavioral pathology due to 22q11 deletion has a distinct in vivo signature.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13602371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148276233","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

PolyQ-expanded ataxin-3 is associated with mitochondrial alterations in Machado-Joseph disease. polyq扩增的ataxin-3与Machado-Joseph病的线粒体改变有关

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-09-01 Epub Date: 2026-09-18 DOI: 10.1242/dmm.052757

Ignacio Simó, Katherine J Robinson, Julia Y Kam, Yvonne Wang, Andrea Kuriakose, Esmeralda Paric, Flora Cheng, Anastasiya Potapenko, Yousun An, Maxinne Watchon, Albert Lee, Angela S Laird

{"title":"PolyQ-expanded ataxin-3 is associated with mitochondrial alterations in Machado-Joseph disease.","authors":"Ignacio Simó, Katherine J Robinson, Julia Y Kam, Yvonne Wang, Andrea Kuriakose, Esmeralda Paric, Flora Cheng, Anastasiya Potapenko, Yousun An, Maxinne Watchon, Albert Lee, Angela S Laird","doi":"10.1242/dmm.052757","DOIUrl":"10.1242/dmm.052757","url":null,"abstract":"Spinocerebellar ataxia type 3, also known as Machado-Joseph disease (MJD), is a fatal neurodegenerative disease caused by an expanded CAG repeat in ataxin-3 (ATXN3). Here, we investigated mitochondrial alterations across complementary MJD models, including transgenic zebrafish, CMVMJD135 mice and primary neuronal cultures. Proteomic profiling of brain lysates from male and female wild-type and CMVMJD135 mice identified mitochondrial alterations and altered oxidative phosphorylation-associated protein abundance as major shared features in both male and female MJD mice. Primary neuron cultures derived from CMVMJD135 mice were examined, validating the proteomic findings and revealing alterations in mitochondrial morphology. We further examined a transgenic zebrafish model of MJD that expresses EGFP-fused human ataxin-3 containing 84 glutamines in neurons (driven by the pan-neuronal elavl3/HuC promoter). The MJD zebrafish model also exhibited altered levels of mitochondrial electron transport chain complex proteins and enhanced sensitivity to rotenone. Notably, complex II-associated alterations featured across most assays, supporting complex II-linked dysregulation as a convergent, potentially targetable component of MJD. These phenotypes provide a robust platform for evaluating potential mitochondrial-targeted therapies and support growing evidence that disrupted mitochondrial homeostasis contributes to MJD pathogenesis.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":"19 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13617979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988681","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

Zebrafish against cancer: towards clinical relevance. 斑马鱼抗癌：走向临床意义。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-09-01 Epub Date: 2026-09-28 DOI: 10.1242/dmm.053145

Gabriel Forn-Cuni, Bruno Lopes-Bastos, David M Langenau, E Elizabeth Patton, B Ewa Snaar-Jagalska

引用次数: 0

An improved Sms p.Gly56Ser model of Snyder-Robinson syndrome reveals phenotypic parallels with clinical features. 改进的SMS p.Gly56Ser小鼠模型揭示了表型与临床特征的相似之处。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-09-01 Epub Date: 2026-09-23 DOI: 10.1242/dmm.052953

Tracy Murray Stewart, Saurabh Tata, Pierre-Alexandre Piec, Jackson R Foley, Teri Koerner, Mary Jo Kutler, Anthony E Pegg, Charles E Schwartz, Robert A Casero, Aamir Zuberi, Cathleen Lutz, Maximiliano Presa

{"title":"An improved Sms p.Gly56Ser model of Snyder-Robinson syndrome reveals phenotypic parallels with clinical features.","authors":"Tracy Murray Stewart, Saurabh Tata, Pierre-Alexandre Piec, Jackson R Foley, Teri Koerner, Mary Jo Kutler, Anthony E Pegg, Charles E Schwartz, Robert A Casero, Aamir Zuberi, Cathleen Lutz, Maximiliano Presa","doi":"10.1242/dmm.052953","DOIUrl":"10.1242/dmm.052953","url":null,"abstract":"Snyder-Robinson syndrome (SRS) is a rare X-linked disorder, caused by pathogenic variants in spermine synthase (SMS), associated with spermine deficiency and excessive spermidine accumulation. Previously reported mouse models exhibited reduced birthrate and survival of affected males, greatly limiting their experimental utility. Here, we describe a new mouse model, carrying the clinically relevant Sms p.Gly56Ser (SmsG56S) allele, in which viable males are recovered at Mendelian ratios, enabling generation of adequately powered cohorts. Hemizygous males produced markedly reduced SMS protein across tissues, recreating the biochemical hallmark of SRS, an elevated spermidine:spermine ratio. SmsG56S/Y males exhibited reduced body size, altered body composition, decreased locomotor and exploratory behaviors, and reduced seizure threshold, aligning with clinical features reported in patients with SRS. Serum low-density lipoprotein, high-density lipoprotein and cholesterol levels were reduced, while brain histology revealed modest region-specific astrocytic changes. Comprehensive polyamine profiling revealed tissue-specific biochemical disturbances, highlighting putrescine elevation in the brain and informing the development of translational strategies and windows for intervention. Overall, this improved model reproduces multiple key aspects of the human SRS phenotype and provides a robust platform for mechanistic studies and preclinical evaluation of therapies.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148629850","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

Glial ceramide orchestrates lipid homeostasis and age-dependent motor function. 胶质神经酰胺协调脂质稳态和年龄依赖的运动功能。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-08-24 DOI: 10.1242/dmm.052840

Lovleen Garg, Karthik H, Aakash Chandramouli, Senthilkumar D, Siddhesh Kamat, Anuradha Ratnaparkhi, Girish Ratnaparkhi

{"title":"Glial ceramide orchestrates lipid homeostasis and age-dependent motor function.","authors":"Lovleen Garg, Karthik H, Aakash Chandramouli, Senthilkumar D, Siddhesh Kamat, Anuradha Ratnaparkhi, Girish Ratnaparkhi","doi":"10.1242/dmm.052840","DOIUrl":"https://doi.org/10.1242/dmm.052840","url":null,"abstract":"Glial cells have emerged as equal partners to neurons in the development and maintenance of the nervous system. In this study, we examine the consequences of modulating glial ceramide metabolism on adult motor function. Glial reduction of ER-localised ceramide synthesis, as exemplified by knockdown (KD) of schlank or ifc or lace, leads to age-dependent motor defects, as does KD of ceramide transfer protein (CERT). Motor defects in CERT-null animals can be significantly rescued by glial CERT expression, further highlighting the importance of glial ceramide homeostasis. Expectedly, glial schlank KD and CERT KD lead to lipid modulation in the brain, characterised by decreased ceramide phosphoethanolamine, increased ceramide phosphates and triacylglycerols, as measured by lipid mass spectrometry, and intriguingly, decreased Lipid Droplet (LD) size and density. Further, disruption of CERT's interaction with the ER-tethering protein VAPB also affects LD dynamics. Our research implicates the glial sphingolipid pathway as an important determinant of age-dependent adult motor function, with LDs serving as a sensitive diagnostic readout. As such, our study has implications for a host of human motor neuron diseases with late-onset motor deficits.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808478","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

UBA1 knockdown dysregulates UBA1-sensitive proteins and impairs muscle function in models of spinal muscular atrophy X-linked 2. 在果蝇和小鼠中，UBA1敲低会失调UBA1敏感蛋白的水平并损害肌肉功能。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-08-01 Epub Date: 2026-08-26 DOI: 10.1242/dmm.052935

Michelle Curley, Flavia A Graca, Anna Stephan, Wei Wang, Vishwajeeth R Pagala, Yong-Dong Wang, Anthony A High, Fabio Demontis

{"title":"UBA1 knockdown dysregulates UBA1-sensitive proteins and impairs muscle function in models of spinal muscular atrophy X-linked 2.","authors":"Michelle Curley, Flavia A Graca, Anna Stephan, Wei Wang, Vishwajeeth R Pagala, Yong-Dong Wang, Anthony A High, Fabio Demontis","doi":"10.1242/dmm.052935","DOIUrl":"10.1242/dmm.052935","url":null,"abstract":"UBA1 is the primary ubiquitin-activating enzyme that initiates ubiquitination, which regulates protein function and turnover. Although UBA1 loss is cell lethal, silent mutations that reduce UBA1 mRNA levels cause spinal muscular atrophy X-linked 2 (SMAX2), a disorder marked by skeletal muscle weakness and wasting. However, it remains unexplored how UBA1 impacts the muscle proteome, and whether muscle weakness can arise from reducing UBA1 function solely in skeletal muscle. Here, we examined Drosophila and mice with muscle-targeted UBA1 knockdown and found that this intervention reduced protein ubiquitination, muscle function and lifespan. Integrated transcriptomic and proteomic analyses indicated that a limited set of proteins is modulated post-transcriptionally by Uba1 RNA interference (Uba1RNAi), suggesting that these UBA1-sensitive proteins rely on optimal UBA1 levels for degradation (Uba1RNAi-upregulated proteins) and stability (Uba1RNAi-downregulated proteins). Therefore, despite the general function of UBA1 in ubiquitination, UBA1 knockdown alters the levels of relatively few critical proteins, which may contribute to muscle weakness and SMAX2 pathogenesis. Moreover, although SMAX2-linked UBA1 mutations occur ubiquitously, experimental reduction of UBA1 function solely in skeletal muscle recapitulates key disease aspects, highlighting a possible muscle-centric origin of SMAX2.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148390200","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

Placental defects revealed by modelling Prader-Willi syndrome in mice. 小鼠PWS模型所揭示的胎盘缺陷。

IF 3.6 3区医学

Disease Models & Mechanisms Pub Date : 2026-08-01 Epub Date: 2026-09-01 DOI: 10.1242/dmm.052833

Anna E Webberley, Raquel Boque-Sastre, Lauren Bailey, Cerys Charles, Rachel A Jones, Rosie Bunton-Stasyshyn, Michelle E Stewart, Sara E Wells, David S Chatelet, Stephanie K Robinson, Matthew J Higgs, Rosalind M John, Anthony R Isles

{"title":"Placental defects revealed by modelling Prader-Willi syndrome in mice.","authors":"Anna E Webberley, Raquel Boque-Sastre, Lauren Bailey, Cerys Charles, Rachel A Jones, Rosie Bunton-Stasyshyn, Michelle E Stewart, Sara E Wells, David S Chatelet, Stephanie K Robinson, Matthew J Higgs, Rosalind M John, Anthony R Isles","doi":"10.1242/dmm.052833","DOIUrl":"10.1242/dmm.052833","url":null,"abstract":"The neurodevelopmental disorder Prader-Willi syndrome (PWS) is caused by paternally derived loss of gene expression from the imprinted interval on chromosome 15q11-q13. Recently, it has been suggested that the abnormal feeding-related behaviours characteristic of PWS can, in part, be developmentally programmed in utero via abnormal placental function. Here, we report that several PWS-associated genes were expressed in mouse placenta with three PWS-associated RNA transcripts, i.e. genes Magel2 and Necdin, and the lncRNA Sngh14, colocalised to the Kdr-positive (Kdr+) foetal endothelial cells of the labyrinth zone central to nutrient transport. In a novel PWS mouse model (Large+/-) we found markedly reduced expression of PWS-associated genes in the placenta and an associated ∼25% reduction in Kdr+ foetal endothelial cells. Although this did not directly translate into a significant reduction in foetal growth late in gestation, these data suggest that placental function and nutrient transfer from mother to foetus could be compromised in PWS contributing to later post-natal phenotypes.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13580601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396318","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