Disease Models & Mechanisms最新文献_第10页

Modelling the micro- and macro- environment of pancreatic cancer: from patients to pre-clinical models and back. 胰腺癌微观和宏观环境建模：从患者到临床前模型再到临床前模型。

IF 4.3 3区医学

Disease Models & Mechanisms Pub Date : 2024-04-19 DOI: 10.1242/dmm.050624

Eloise G Lloyd, Joaquín Araos Henríquez, Giulia Biffi

引用次数: 0

Improving access to gene therapy for rare diseases. 改善罕见病基因治疗的可及性。

IF 4.3 3区医学

Disease Models & Mechanisms Pub Date : 2024-04-19 DOI: 10.1242/dmm.050623

Thomas A Fox, Claire Booth

引用次数: 0

Striatal parvalbumin interneurons, not cholinergic interneurons, are activated in a mouse model of cerebellar dystonia. 在小脑肌张力障碍小鼠模型中，纹状体旁白质中间神经元而非胆碱能中间神经元被激活。

IF 4.3 3区医学

Disease Models & Mechanisms Pub Date : 2024-04-15 DOI: 10.1242/dmm.050338

Taku Matsuda, Ryoma Morigaki, Hiroaki Hayasawa, Hiroshi Koyama, Teruo Oda, Kazuhisa Miyake, Yasushi Takagi

{"title":"Striatal parvalbumin interneurons, not cholinergic interneurons, are activated in a mouse model of cerebellar dystonia.","authors":"Taku Matsuda, Ryoma Morigaki, Hiroaki Hayasawa, Hiroshi Koyama, Teruo Oda, Kazuhisa Miyake, Yasushi Takagi","doi":"10.1242/dmm.050338","DOIUrl":"https://doi.org/10.1242/dmm.050338","url":null,"abstract":"Dystonia is supposed to arise from abnormalities in the motor loop of the basal ganglia; however, there is an ongoing debate regarding cerebellar involvement. We adopted the established cerebellar dystonia mice model by injecting ouabain to examine the contribution of the cerebellum. Initially, we examined whether the entopeduncular nucleus (EPN), substantia nigra pars reticulata (SNr), globus pallidus externus (GPe), and striatal neurons were activated in the model. Next, we examined whether dopamine D1 receptor agonists (D1 agonist) and dopamine D2 receptor antagonists (D2 antagonist) or selective ablation of striatal parvalbumin (PV) interneurons could modulate their involuntary movements. The cerebellar dystonia mice had a higher number of c-fos-positive cells in the EPN, SNr, and GPe, as well as a higher positive ratio of c-fos in striatal PV interneurons than the control mice. Furthermore, systemic administration of combined D1 agonist and D2 antagonist and selective ablation of striatal PV interneurons relieved their involuntary movements. Abnormalities in the motor loop of the basal ganglia could be crucially involved in cerebellar dystonia, and modulating PV interneurons might provide a novel treatment strategy.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140591639","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

Caspase-resistant ROCK1 expression prolongs survival of Eµ-Myc B cell lymphoma mice. 抗Caspase的ROCK1表达可延长Eµ-Myc B细胞淋巴瘤小鼠的存活期。

IF 4.3 3区医学

Disease Models & Mechanisms Pub Date : 2024-04-15 DOI: 10.1242/dmm.050631

Katerina Mardilovich, Gregory Naylor, Linda Julian, Narisa Phinichkusolchit, Karen Keeshan, Karen Blyth, Michael F Olson

{"title":"Caspase-resistant ROCK1 expression prolongs survival of Eµ-Myc B cell lymphoma mice.","authors":"Katerina Mardilovich, Gregory Naylor, Linda Julian, Narisa Phinichkusolchit, Karen Keeshan, Karen Blyth, Michael F Olson","doi":"10.1242/dmm.050631","DOIUrl":"https://doi.org/10.1242/dmm.050631","url":null,"abstract":"Apoptosis is characterized by membrane blebbing and apoptotic body formation. Caspase cleavage of ROCK1 generates an active fragment that promotes actin-myosin mediated contraction and membrane blebbing during apoptosis. Expression of caspase-resistant non-cleavable ROCK1 (Rock1 NC) prolonged survival of mice that rapidly develop B cell lymphomas due to Eµ-Myc transgene expression. Eµ-Myc; Rock1 NC mice had significantly fewer bone marrow cells relative to Eµ-Myc mice expressing wild-type ROCK1 (Rock1 WT), which was associated with altered cell cycle profiles. Circulating macrophage numbers were lower in Eµ-Myc; Rock1 NC mice, but there were higher levels of bone marrow macrophages, consistent with spontaneous cell death in Eµ-Myc; Rock1 NC mice bone marrows being more inflammatory. Rock1 WT recipient mice transplanted with pre-neoplastic Eµ-Myc; Rock1 NC bone marrow cells survived longer than mice transplanted with Eµ-Myc; Rock1 WT cells, indicating that the survival benefit was intrinsic to the Eµ-Myc; Rock1 NC bone marrow cells. The results suggest that the apoptotic death of Eµ-Myc; Rock1 NC cells generates a proliferation-suppressive microenvironment in bone marrows that reduces cell numbers and prolongs B cell lymphoma mouse survival.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140591641","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

The effect of bone marrow derived cell therapies on hind limb perfusion, A systematic review and meta-analysis. 骨髓细胞疗法对后肢灌注的影响，系统回顾与荟萃分析。

IF 4.3 3区医学

Disease Models & Mechanisms Pub Date : 2024-04-15 DOI: 10.1242/dmm.050632

F C C van Rhijn-Brouwer, K E Wever, R Kiffen, J R van Rhijn, H Gremmels, J O Fledderus, R W M Vernooij, M C Verhaar

引用次数: 0

Missense mutation (C667F) in murine β-dystroglycan causes embryonic lethality, myopathy and blood-brain barrier destabilization. 小鼠β-肌收缩蛋白的错义突变（C667F）会导致胚胎死亡、肌病和血脑屏障失稳。

IF 4.3 3区医学

Disease Models & Mechanisms Pub Date : 2024-04-15 DOI: 10.1242/dmm.050594

Rui Lois Tan, Francesca Sciandra, Wolfgang Hübner, Manuela Bozzi, Jens Reimann, Susanne Schoch, Andrea Brancaccio, Sandra Blaess

{"title":"Missense mutation (C667F) in murine β-dystroglycan causes embryonic lethality, myopathy and blood-brain barrier destabilization.","authors":"Rui Lois Tan, Francesca Sciandra, Wolfgang Hübner, Manuela Bozzi, Jens Reimann, Susanne Schoch, Andrea Brancaccio, Sandra Blaess","doi":"10.1242/dmm.050594","DOIUrl":"https://doi.org/10.1242/dmm.050594","url":null,"abstract":"Dystroglycan (DG) is an extracellular matrix receptor consisting of an α- and a β-DG subunit encoded by the DAG1 gene. The homozygous mutation (c.2006G>T, p.Cys669Phe) in β-DG causes Muscle-Eye-Brain disease with multicystic leukodystrophy in humans. In a mouse model of this primary dystroglycanopathy, approximately two-thirds of homozygous embryos fail to develop to term. Mutant mice that are born undergo a normal postnatal development but show a late-onset myopathy with partially penetrant histopathological changes and an impaired performance on an activity wheel. Their brains and eyes are structurally normal, but the localization of mutant β-DG is altered in the glial perivascular endfeet resulting in a perturbed protein composition of the blood-brain and blood-retina barrier. In addition, α- and β-DG protein levels are significantly reduced in muscle and brain of mutant mice. Due to the partially penetrant developmental phenotype of the C669F-β-DG mice, they represent a novel and highly valuable mouse model to study the molecular effects of β-DG functional alterations both during embryogenesis and in mature muscle, brain and eye, and to gain insight into the pathogenesis of primary dystroglycanopathies.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140592064","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

Promoting mitochondrial dynamics by inhibiting the PINK1/PRKN pathway to relieve diabetic nephropathy. 通过抑制 PINK1/PRKN 通路促进线粒体活力，缓解糖尿病肾病。

IF 4.3 3区医学

Disease Models & Mechanisms Pub Date : 2024-04-11 DOI: 10.1242/dmm.050471

Jun-Yi Zhu, Joyce van de Leemput, Zhe Han

{"title":"Promoting mitochondrial dynamics by inhibiting the PINK1/PRKN pathway to relieve diabetic nephropathy.","authors":"Jun-Yi Zhu, Joyce van de Leemput, Zhe Han","doi":"10.1242/dmm.050471","DOIUrl":"https://doi.org/10.1242/dmm.050471","url":null,"abstract":"Diabetes is a metabolic disorder characterized by high blood glucose levels and is a leading cause of kidney disease. Diabetic nephropathy has been attributed to dysfunctional mitochondria. However, many questions remain about the exact mechanism. The structure, function, and molecular pathways between mammalian podocytes and Drosophila nephrocytes are highly conserved, therefore we used flies on a high-sucrose diet to model type 2 diabetic nephropathy. The nephrocytes of high-sucrose diet flies showed significant functional decline and decreased cell size, associated with a shortened lifespan. Structurally, the nephrocytes filtration structure known as the slit diaphragm was disorganized. At the cellular level, we found altered mitochondrial dynamics and dysfunction. Regulating mitochondrial dynamics by either genetic modification of the Pink1/Park (mammalian PINK1/PRKN) pathway or treatment with BGP-15, mitigated the mitochondrial defects and nephrocyte functional decline. These findings support a role for Pink1/Park-mediated mitophagy and associated control of mitochondrial dynamics, essential for function, in diabetic nephropathy; and demonstrate that targeting this pathway might provide therapeutic benefits in type 2 diabetic nephropathy.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140592148","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

The BALB/c.mdx62 mouse exhibits a dystrophic muscle pathology and is a novel model of Duchenne muscular dystrophy. BALB/c.mdx62 小鼠表现出肌肉萎缩性病理，是杜氏肌营养不良症的新型模型。

IF 4.3 3区医学

Disease Models & Mechanisms Pub Date : 2024-04-11 DOI: 10.1242/dmm.050502

Kristy Swiderski, Audrey S Chan, Marco J Herold, Andrew J Kueh, Jin D Chung, Justin P Hardee, Jennifer Trieu, Annabel Chee, Timur Naim, Paul Gregorevic, Gordon S Lynch

{"title":"The BALB/c.mdx62 mouse exhibits a dystrophic muscle pathology and is a novel model of Duchenne muscular dystrophy.","authors":"Kristy Swiderski, Audrey S Chan, Marco J Herold, Andrew J Kueh, Jin D Chung, Justin P Hardee, Jennifer Trieu, Annabel Chee, Timur Naim, Paul Gregorevic, Gordon S Lynch","doi":"10.1242/dmm.050502","DOIUrl":"https://doi.org/10.1242/dmm.050502","url":null,"abstract":"Duchenne muscular dystrophy (DMD) is a devastating monogenic skeletal muscle wasting disorder. While many pharmacological and genetic interventions have been reported in preclinical studies, few have progressed to clinical trials with meaningful benefit. Identifying therapeutic potential may be limited by availability of suitable preclinical mouse models. More rigorous testing across models with varied background strains and mutations may identify treatments for clinical success. Here we report the generation of a DMD mouse model, with a CRISPR-induced deletion within exon 62 of the Dmd gene, and the first generated in BALB/c mice. Analysis of mice at 3, 6, and 12 months of age confirmed loss of Dp427 protein expression and resultant dystrophic pathology in limb muscles and the diaphragm, with evidence of centrally nucleated fibers, increased inflammatory markers and fibrosis, progressive decline in muscle function, and compromised trabecular bone development. The C.mdx62 mouse is a novel model of DMD with associated variations in the immune response and muscle phenotype, compared with existing models. It represents an important addition to the preclinical model toolbox for developing therapeutic strategies.","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140591967","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: OPA1 deficiency impairs oxidative metabolism in cycling cells, underlining a translational approach for degenerative diseases. 更正：OPA1 缺乏会损害循环细胞中的氧化代谢，强调了一种治疗退行性疾病的转化方法。

IF 4.3 3区医学

Disease Models & Mechanisms Pub Date : 2024-04-01 DOI: 10.1242/dmm.050815

A. Millet, Corentin Coustham, Camille Champigny, Nadege Merabet, Marlène Botella, Christine Demeilliers, Anne Devin, Anne Galinier, Pascale Belenguer, Joel Bordeneuve-Guibé, N. Davezac

引用次数: 0

Dmd mdx mice have defective oligodendrogenesis, delayed myelin compaction and persistent hypomyelination. Dmd mdx 小鼠具有少突生成缺陷、髓鞘压实延迟和持续髓鞘化不足。

IF 4.3 3区医学

Disease Models & Mechanisms Pub Date : 2024-04-01 Epub Date: 2024-05-09 DOI: 10.1242/dmm.050115

Andrea J Arreguin, Zijian Shao, Holly Colognato

{"title":"Dmd mdx mice have defective oligodendrogenesis, delayed myelin compaction and persistent hypomyelination.","authors":"Andrea J Arreguin, Zijian Shao, Holly Colognato","doi":"10.1242/dmm.050115","DOIUrl":"10.1242/dmm.050115","url":null,"abstract":"<p><p>Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene, resulting in the loss of dystrophin, a large cytosolic protein that links the cytoskeleton to extracellular matrix receptors in skeletal muscle. Aside from progressive muscle damage, many patients with DMD also have neurological deficits of unknown etiology. To investigate potential mechanisms for DMD neurological deficits, we assessed postnatal oligodendrogenesis and myelination in the Dmdmdx mouse model. In the ventricular-subventricular zone (V-SVZ) stem cell niche, we found that oligodendrocyte progenitor cell (OPC) production was deficient, with reduced OPC densities and proliferation, despite a normal stem cell niche organization. In the Dmdmdx corpus callosum, a large white matter tract adjacent to the V-SVZ, we also observed reduced OPC proliferation and fewer oligodendrocytes. Transmission electron microscopy further revealed significantly thinner myelin, an increased number of abnormal myelin structures and delayed myelin compaction, with hypomyelination persisting into adulthood. Our findings reveal alterations in oligodendrocyte development and myelination that support the hypothesis that changes in diffusion tensor imaging seen in patients with DMD reflect developmental changes in myelin architecture.</p>","PeriodicalId":11144,"journal":{"name":"Disease Models & Mechanisms","volume":null,"pages":null},"PeriodicalIF":4.3,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11095635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140891813","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