Mouse models of myocardial infarction: comparing permanent ligation and ischaemia-reperfusion [SPECIAL ARTICLE]
ABSTRACT Myocardial infarction (MI) is a disease of major consequence in the modern world, causing permanent, irreversible damage to the heart. Survivors are at risk for developing further cardiovascular pathologies such as heart failure. Further study of MI injury is crucial to improve the understanding and treatment of the post-MI heart. The most commonly used model for MI in vivo is surgical ligation of the left anterior descending coronary artery (LAD). There are two predominant approaches: permanent ligation (PL), where the LAD is permanently occluded with a suture, or ischaemia-reperfusion (IR), where the LAD is temp...
Source: DMM Disease Models and Mechanisms - November 18, 2020 Category: Biomedical Science Authors: De Villiers, C., Riley, P. R. Tags: Tools and Resources for Mouse Studies SPECIAL ARTICLE Source Type: research

Imbalanced cellular metabolism compromises cartilage homeostasis and joint function in a mouse model of mucolipidosis type III gamma [RESEARCH ARTICLE]
This article has an associated First Person interview with the first author of the paper. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - November 18, 2020 Category: Biomedical Science Authors: Westermann, L. M., Fleischhauer, L., Vogel, J., Jenei-Lanzl, Z., Ludwig, N. F., Schau, L., Morellini, F., Baranowsky, A., Yorgan, T. A., Di Lorenzo, G., Schweizer, M., de Souza Pinheiro, B., Guarany, N. R., Sperb-Ludwig, F., Visioli, F., Oliveira Silva, T Tags: Rare diseases RESEARCH ARTICLE Source Type: research

First person - Melanie Gartz [FIRST PERSON]
ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping early-career researchers promote themselves alongside their papers. Melanie Gartz is first author on ‘Duchenne muscular dystrophy (DMD) cardiomyocyte-secreted exosomes promote the pathogenesis of DMD-associated cardiomyopathy’, published in DMM. Melanie conducted the research described in this article while a graduate student in Jennifer Strande's lab at the Medical College of Wisconsin, Cardiovascular Research Center, Milwaukee, WI, USA. She is now a postdoctoral...
Source: DMM Disease Models and Mechanisms - November 13, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

Duchenne muscular dystrophy (DMD) cardiomyocyte-secreted exosomes promote the pathogenesis of DMD-associated cardiomyopathy [RESEARCH ARTICLE]
This article has an associated First Person interview with the first author of the paper. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - November 13, 2020 Category: Biomedical Science Authors: Gartz, M., Lin, C.-W., Sussman, M. A., Lawlor, M. W., Strande, J. L. Tags: Stem Cells, Neuromuscular RESEARCH ARTICLE Source Type: research

Ammonia inhibits energy metabolism in astrocytes in a rapid and glutamate dehydrogenase 2-dependent manner [RESEARCH ARTICLE]
ABSTRACT Astrocyte dysfunction is a primary factor in hepatic encephalopathy (HE) impairing neuronal activity under hyperammonemia. In particular, the early events causing ammonia-induced toxicity to astrocytes are not well understood. Using established cellular HE models, we show that mitochondria rapidly undergo fragmentation in a reversible manner upon hyperammonemia. Further, in our analyses, within a timescale of minutes, mitochondrial respiration and glycolysis were hampered, which occurred in a pH-independent manner. Using metabolomics, an accumulation of glucose and numerous amino acids, including branched chain am...
Source: DMM Disease Models and Mechanisms - November 4, 2020 Category: Biomedical Science Authors: Drews, L., Zimmermann, M., Westhoff, P., Brilhaus, D., Poss, R. E., Bergmann, L., Wiek, C., Brenneisen, P., Piekorz, R. P., Mettler-Altmann, T., Weber, A. P. M., Reichert, A. S. Tags: RESEARCH ARTICLE Source Type: research

First person - Zakia Abdelhamed [FIRST PERSON]
ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping early-career researchers promote themselves alongside their papers. Zakia Abdelhamed is first author on ‘A novel hypomorphic allele of Spag17 causes primary ciliary dyskinesia phenotypes in mice’, published in DMM. Zakia is a research associate in the lab of Dr Rolf Stottmann at Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA, investigating animal models that recapitulate a human condition for understanding disease pathogenesis. (Source: DMM Dis...
Source: DMM Disease Models and Mechanisms - October 30, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

First person - Gabriel Matos-Rodrigues [FIRST PERSON]
ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping early-career researchers promote themselves alongside their papers. Gabriel Matos-Rodrigues is first author on ‘Progenitor death drives retinal dysplasia and neuronal degeneration in a mouse model of ATRIP-Seckel syndrome’, published in DMM. Gabriel conducted the research described in this article while a PhD student in Rodrigo A. P. Martins's lab at Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. He is now a PhD student in the lab of Bernard S. Lo...
Source: DMM Disease Models and Mechanisms - October 30, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

Cells expressing PAX8 are the main source of homeostatic regeneration of adult mouse endometrial epithelium and give rise to serous endometrial carcinoma [RESEARCH ARTICLE]
ABSTRACT Humans and mice have cyclical regeneration of the endometrial epithelium. It is expected that such regeneration is ensured by tissue stem cells, but their location and hierarchy remain debatable. A number of recent studies have suggested the presence of stem cells in the mouse endometrial epithelium. At the same time, it has been reported that this tissue can be regenerated by stem cells of stromal/mesenchymal or bone marrow cell origin. Here, we describe a single-cell transcriptomic atlas of the main cell types of the mouse uterus and epithelial subset transcriptome and evaluate the contribution of epithelial cel...
Source: DMM Disease Models and Mechanisms - October 30, 2020 Category: Biomedical Science Authors: Fu, D.-J., De Micheli, A. J., Bidarimath, M., Ellenson, L. H., Cosgrove, B. D., Flesken-Nikitin, A., Nikitin, A. Y. Tags: Cancer RESEARCH ARTICLE Source Type: research

Progenitor death drives retinal dysplasia and neuronal degeneration in a mouse model of ATRIP-Seckel syndrome [RESEARCH ARTICLE]
This article has an associated First Person interview with the first author of the paper. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - October 30, 2020 Category: Biomedical Science Authors: Matos-Rodrigues, G. E., Tan, P. B., Rocha-Martins, M., Charlier, C. F., Gomes, A. L., Cabral-Miranda, F., Grigaravicius, P., Hofmann, T. G., Frappart, P.-O., Martins, R. A. P. Tags: Developmental Disorders RESEARCH ARTICLE Source Type: research

Chronic administration of P2X7 receptor antagonist JNJ-47965567 delays disease onset and progression, and improves motor performance in ALS SOD1G93A female mice [RESEARCH ARTICLE]
ABSTRACT Neuroinflammation is one of the main physiopathological mechanisms of amyotrophic lateral sclerosis (ALS), produced by the chronic activation of microglia in the CNS. This process is triggered by the persistent activation of the ATP-gated P2X7 receptor (P2RX7, hereafter referred to as P2X7R). The present study aimed to evaluate the effects of the chronic treatment with the P2X7R antagonist JNJ-47965567 in the development and progression of ALS in the SOD1G93A murine model. SOD1G93A mice were intraperitoneally (i.p.) injected with either 30 mg/kg of JNJ-47965567 or vehicle 4 times per week, from pre-onset age ...
Source: DMM Disease Models and Mechanisms - October 30, 2020 Category: Biomedical Science Authors: Ruiz-Ruiz, C., Garcia-Magro, N., Negredo, P., Avendano, C., Bhattacharya, A., Ceusters, M., Garcia, A. G. Tags: Neuromuscular RESEARCH ARTICLE Source Type: research

A novel hypomorphic allele of Spag17 causes primary ciliary dyskinesia phenotypes in mice [RESEARCH ARTICLE]
This article has an associated First Person interview with the first author of the paper. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - October 30, 2020 Category: Biomedical Science Authors: Abdelhamed, Z., Lukacs, M., Cindric, S., Omran, H., Stottmann, R. W. Tags: Developmental Disorders RESEARCH ARTICLE Source Type: research

Cellular and animal models for facioscapulohumeral muscular dystrophy [REVIEW]
ABSTRACT Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common forms of muscular dystrophy and presents with weakness of the facial, scapular and humeral muscles, which frequently progresses to the lower limbs and truncal areas, causing profound disability. Myopathy results from epigenetic de-repression of the D4Z4 microsatellite repeat array on chromosome 4, which allows misexpression of the developmentally regulated DUX4 gene. DUX4 is toxic when misexpressed in skeletal muscle and disrupts several cellular pathways, including myogenic differentiation and fusion, which likely underpins pathology. DUX4 an...
Source: DMM Disease Models and Mechanisms - October 28, 2020 Category: Biomedical Science Authors: DeSimone, A. M., Cohen, J., Lek, M., Lek, A. Tags: Neuromuscular, Model Systems in Drug Discovery REVIEW Source Type: research

An HIV-Tat inducible mouse model system of childhood HIV-associated nephropathy [RESEARCH ARTICLE]
ABSTRACT Modern antiretroviral therapies (ART) have decreased the prevalence of HIV-associated nephropathy (HIVAN). Nonetheless, we continue to see children and adolescents with HIVAN all over the world. Furthermore, once HIVAN is established in children, it is difficult to revert its long-term progression, and we need better animal models of childhood HIVAN to test new treatments. To define whether the HIV-1 trans-activator (Tat) gene precipitates HIVAN in young mice, and to develop an inducible mouse model of childhood HIVAN, an HIV-Tat gene cloned from a child with HIVAN was used to generate recombinant adenoviral vecto...
Source: DMM Disease Models and Mechanisms - October 28, 2020 Category: Biomedical Science Authors: Tang, P., Das, J. R., Li, J., Yu, J., Ray, P. E. Tags: Model Systems in Drug Discovery RESEARCH ARTICLE Source Type: research

Modeling neurodegeneration in Caenorhabditis elegans [AT A GLANCE]
ABSTRACT The global burden of neurodegenerative diseases underscores the urgent need for innovative strategies to define new drug targets and disease-modifying factors. The nematode Caenorhabditis elegans has served as the experimental subject for multiple transformative discoveries that have redefined our understanding of biology for ~60 years. More recently, the considerable attributes of C. elegans have been applied to neurodegenerative diseases, including amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease and Huntington's disease. Transgenic nematodes with genes encoding normal and disease var...
Source: DMM Disease Models and Mechanisms - October 26, 2020 Category: Biomedical Science Authors: Caldwell, K. A., Willicott, C. W., Caldwell, G. A. Tags: Neurodegenerative disorders, C. elegans, Model Systems in Drug Discovery AT A GLANCE Source Type: research

First person - Gideon Hughes [FIRST PERSON]
ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping early-career researchers promote themselves alongside their papers. Gideon Hughes is first author on ‘Machine learning discriminates a movement disorder in a zebrafish model of Parkinson's disease’, published in DMM. Gideon conducted the research described in this article while a PhD student in Betsy Pownall's lab at the University of York, York, UK. He is now a postdoc in the lab of Henry Roehl at the University of Sheffield, Sheffield, UK, using the zebrafish as...
Source: DMM Disease Models and Mechanisms - October 16, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research