The latest from the preLights community - September 2019 [PREPRINT HIGHLIGHTS]
(Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - September 27, 2019 Category: Biomedical Science Tags: PREPRINT HIGHLIGHTS Source Type: research

First person - Karishma Chhabria [FIRST PERSON]
ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms (DMM), helping early-career researchers promote themselves alongside their papers. Karishma Chhabria is first author on ‘Sodium nitroprusside prevents the detrimental effects of glucose on the neurovascular unit and behaviour in zebrafish’, published in DMM. Karishma conducted the research described in this article while a PhD student in Tim Chico and Clare Howarth's lab at University of Sheffield, UK. She is now a postdoc in the lab of David Kleinfeld at UCSD, USA, invest...
Source: DMM Disease Models and Mechanisms - September 25, 2019 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

Sodium nitroprusside prevents the detrimental effects of glucose on the neurovascular unit and behaviour in zebrafish [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 - September 25, 2019 Category: Biomedical Science Authors: Chhabria, K., Vouros, A., Gray, C., MacDonald, R. B., Jiang, Z., Wilkinson, R. N., Plant, K., Vasilaki, E., Howarth, C., Chico, T. J. A. Tags: Metabolic Disorders, Zebrafish as a Disease Model RESEARCH ARTICLE Source Type: research

First person - Eleftheria Pervolaraki [FIRST PERSON]
ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms (DMM), helping early-career researchers promote themselves alongside their papers. Eleftheria Pervolaraki is first author on ‘Insoluble Aβ overexpression in an App knock-in mouse model alters microstructure and gamma oscillations in the prefrontal cortex, affecting anxiety-related behaviours’, published in DMM. Eleftheria conducted the research described in this article while a Research Fellow at the School of Biomedical Sciences, University of Leeds, UK. She is now M...
Source: DMM Disease Models and Mechanisms - September 24, 2019 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

Insoluble A{beta} overexpression in an App knock-in mouse model alters microstructure and gamma oscillations in the prefrontal cortex, affecting anxiety-related behaviours [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 - September 24, 2019 Category: Biomedical Science Authors: Pervolaraki, E., Hall, S. P., Foresteire, D., Saito, T., Saido, T. C., Whittington, M. A., Lever, C., Dachtler, J. Tags: Neurodegenerative disorders RESEARCH ARTICLE Source Type: research

Therapeutic targeting of Notch signaling and immune checkpoint blockade in a spontaneous, genetically heterogeneous mouse model of T-cell acute lymphoblastic leukemia [RESEARCH ARTICLE]
ABSTRACT T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic cancer derived from the malignant transformation of T-cell progenitors. Outcomes remain poor for T-ALL patients who have either primary resistance to standard-of-care chemotherapy or disease relapse. Notably, there are currently no targeted therapies available in T-ALL. This lack of next-generation therapies highlights the need for relevant preclinical disease modeling to identify and validate new targets and treatment approaches. Here, we adapted a spontaneously arising, genetically heterogeneous, thymic transplantation-based murine model of...
Source: DMM Disease Models and Mechanisms - September 16, 2019 Category: Biomedical Science Authors: Gao, J., Van Meter, M., Hernandez Lopez, S., Chen, G., Huang, Y., Ren, S., Zhao, Q., Rojas, J., Gurer, C., Thurston, G., Kuhnert, F. Tags: Cancer RESEARCH ARTICLE Source Type: research

First person - Tamio Furuse and Hiroshi Mizuma [FIRST PERSON]
ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms (DMM), helping early-career researchers promote themselves alongside their papers. Tamio Furuse and Hiroshi Mizuma are co-first authors on ‘ A new mouse model of GLUT1 deficiency syndrome exhibits abnormal sleep-wake patterns and alterations of glucose kinetics in the brain’, published in DMM. Tamio is a research and development scientist in the lab of Masaru Tamura at RIKEN BioResource Research Center, Japan, investigating the development of a new phenotyping platform of ...
Source: DMM Disease Models and Mechanisms - September 12, 2019 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

First person - Katja Graf and Antonia Last [FIRST PERSON]
ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms (DMM), helping early-career researchers promote themselves alongside their papers. Katja Graf and Antonia Last are co-first authors on ‘ Keeping Candida commensal: how lactobacilli antagonize pathogenicity of Candida albicans in an in vitro gut model’, published in DMM. Katja is a postdoc and Antonia is a PhD student in the lab of Bernhard Hube at the Hans KnoĢˆll Institute (HKI) investigating molecular pathogenicity mechanisms. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - September 12, 2019 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

Keeping Candida commensal: how lactobacilli antagonize pathogenicity of Candida albicans in an in vitro gut model [RESEARCH ARTICLE]
This article has an associated First Person interview with the joint first authors of the paper. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - September 12, 2019 Category: Biomedical Science Authors: Graf, K., Last, A., Gratz, R., Allert, S., Linde, S., Westermann, M., Gröger, M., Mosig, A. S., Gresnigt, M. S., Hube, B. Tags: Microbiome RESEARCH ARTICLE Source Type: research

A new mouse model of GLUT1 deficiency syndrome exhibits abnormal sleep-wake patterns and alterations of glucose kinetics in the brain [RESEARCH ARTICLE]
This article has an associated First Person interview with the joint first authors of the paper. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - September 12, 2019 Category: Biomedical Science Authors: Furuse, T., Mizuma, H., Hirose, Y., Kushida, T., Yamada, I., Miura, I., Masuya, H., Funato, H., Yanagisawa, M., Onoe, H., Wakana, S. Tags: Metabolic Disorders RESEARCH ARTICLE Source Type: research

Experimental models and tools to tackle glioblastoma [REVIEW]
ABSTRACT Glioblastoma multiforme (GBM) is one of the deadliest human cancers. Despite increasing knowledge of the genetic and epigenetic changes that underlie tumour initiation and growth, the prognosis for GBM patients remains dismal. Genome analysis has failed to lead to success in the clinic. Fresh approaches are needed that can stimulate new discoveries across all levels: cell-intrinsic mechanisms (transcriptional/epigenetic and metabolic), cell-cell signalling, niche and microenvironment, systemic signals, immune regulation, and tissue-level physical forces. GBMs are inherently extremely challenging: tumour detection ...
Source: DMM Disease Models and Mechanisms - September 6, 2019 Category: Biomedical Science Authors: Robertson, F. L., Marques-Torrejon, M.-A., Morrison, G. M., Pollard, S. M. Tags: Cancer REVIEW Source Type: research

Modeling hematopoietic disorders in zebrafish [AT A GLANCE]
ABSTRACT Zebrafish offer a powerful vertebrate model for studies of development and disease. The major advantages of this model include the possibilities of conducting reverse and forward genetic screens and of observing cellular processes by in vivo imaging of single cells. Moreover, pathways regulating blood development are highly conserved between zebrafish and mammals, and several discoveries made in fish were later translated to murine and human models. This review and accompanying poster provide an overview of zebrafish hematopoiesis and discuss the existing zebrafish models of blood disorders, such as myeloid and ly...
Source: DMM Disease Models and Mechanisms - September 6, 2019 Category: Biomedical Science Authors: Konantz, M., Schürch, C., Hanns, P., Müller, J. S., Sauteur, L., Lengerke, C. Tags: Zebrafish as a Disease Model AT A GLANCE Source Type: research

First person - Monika J. Tomecka [FIRST PERSON]
ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms (DMM), helping early-career researchers promote themselves alongside their papers. Monika Tomecka is first author on ‘Clinical pathologies of bone fracture modelled in zebrafish’, published in DMM. Monika conducted the research described in this article while a PhD student in Tom Carney's lab at the Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), Singapore and Henry Roehl's lab, Department of Biomedical Science, The Uni...
Source: DMM Disease Models and Mechanisms - September 3, 2019 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

Clinical pathologies of bone fracture modelled in zebrafish [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 - September 3, 2019 Category: Biomedical Science Authors: Tomecka, M. J., Ethiraj, L. P., Sanchez, L. M., Roehl, H. H., Carney, T. J. Tags: Zebrafish as a Disease Model RESEARCH ARTICLE Source Type: research

First person - Tiantian Ji and Lina Zhang [FIRST PERSON]
ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms (DMM), helping early-career researchers promote themselves alongside their papers. Tiantian Ji and Lina Zhang are co-first authors on ‘ Dynamic MAPK signaling activity underlies a transition from growth arrest to proliferation in Drosophila scribble mutant tumors’, published in DMM. Tiantian and Lina are both PhD students in the lab of Yan Yan at The Hong Kong University of Science and Technology Clear Water Bay, Hong Kong. Tiantian is investigating tumor heterogeneity and...
Source: DMM Disease Models and Mechanisms - August 29, 2019 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

Dynamic MAPK signaling activity underlies a transition from growth arrest to proliferation in Drosophila scribble mutant tumors [RESEARCH ARTICLE]
This article has an associated First Person interview with the joint first authors of the paper. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - August 29, 2019 Category: Biomedical Science Authors: Ji, T., Zhang, L., Deng, M., Huang, S., Wang, Y., Pham, T. T., Smith, A. A., Sridhar, V., Cabernard, C., Wang, J., Yan, Y. Tags: Drosophila as a Disease Model RESEARCH ARTICLE Source Type: research

Pramipexole prevents ischemic cell death via mitochondrial pathways in ischemic stroke [RESEARCH ARTICLE]
ABSTRACT A dopamine D2 receptor agonist, pramipexole, has been found to elicit neuroprotection in patients with Parkinson’s disease and restless leg syndrome. Recent evidence has shown that pramipexole mediates its neuroprotection through mitochondria. Considering this, we examined the possible mitochondrial role of pramipexole in promoting neuroprotection following an ischemic stroke of rat. Male Wistar rats underwent transient middle cerebral artery occlusion (tMCAO) and then received pramipexole (0.25 mg and 1 mg/kg body weight) at 1, 6, 12 and 18 h post-occlusion. A panel of neurological tests and ...
Source: DMM Disease Models and Mechanisms - August 29, 2019 Category: Biomedical Science Authors: Andrabi, S. S., Ali, M., Tabassum, H., Parveen, S., Parvez, S. Tags: Rat as a Disease Model RESEARCH ARTICLE Source Type: research

Disease Models & Mechanisms in the Age of Big Data [EDITORIAL]
ABSTRACT In the decade since Disease Models & Mechanisms was launched, the emergence of Big Data as the main foundation of biological information is having a profound effect on how we do research and it has provoked some interesting questions. Is Big Data exploration replacing hypothesis-driven basic research? And, to what extent is disease modeling in the laboratory still relevant to medical research? Recent examples of synergistic approaches utilizing animal modeling and electronic medical records mining show that combining efforts between disease models and clinical datasets can uncover not only disease etiologies, ...
Source: DMM Disease Models and Mechanisms - August 20, 2019 Category: Biomedical Science Authors: Hatzopoulos, A. K. Tags: Editorials Source Type: research

Mast cells enhance sterile inflammation in chronic nonbacterial osteomyelitis [RESEARCH ARTICLE]
ABSTRACT Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease, and patients with active or recurrent bone inflammation at multiple sites are diagnosed with chronic recurrent multifocal osteomyelitis (CRMO). The Chronic multifocal osteomyelitis (CMO) mouse model develops IL-1β-driven sterile bone lesions reminiscent of severe CRMO. The goal of this study was to evaluate the potential involvement of mast cells in CMO/CRMO. Here, we show that mast cells accumulate in inflamed tissues from CMO mice and that mast cell protease Mcpt1 can be detected in the peripheral blood. A transgenic model of conn...
Source: DMM Disease Models and Mechanisms - August 20, 2019 Category: Biomedical Science Authors: Young, S., Sharma, N., Lee, J. H., Chitu, V., Neumeister, V., Sohr, E., Stanley, E. R., Hedrich, C. M., Craig, A. W. B. Tags: RESEARCH ARTICLE Source Type: research

First person - Nicoleta Baxan [FIRST PERSON]
ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms (DMM), helping early-career researchers promote themselves alongside their papers. Nicoleta Baxan is first author on ‘Characterization of acute TLR-7 agonist-induced hemorrhagic myocarditis in mice by multi-parametric quantitative cardiac magnetic resonance imaging’, published in DMM. Nicoleta conducted the research described in this article while in Dr Susanne Sattler's lab at Imperial College London, UK. She is now an MR Physics Research Associate in the lab of Prof. Lan...
Source: DMM Disease Models and Mechanisms - August 16, 2019 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

First person - Eileen Lynch [FIRST PERSON]
ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms (DMM), helping early-career researchers promote themselves alongside their papers. Eileen Lynch is first author on ‘C9ORF72-related cellular pathology in skeletal myocytes derived from ALS-patient induced pluripotent stem cells’, published in DMM. Eileen is a graduate research assistant/PhD candidate in the lab of Masatoshi Suzuki at University of Wisconsin-Madison, WI, USA, investigating in vitro disease modeling of neuromuscular diseases. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - August 16, 2019 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

Characterization of acute TLR-7 agonist-induced hemorrhagic myocarditis in mice by multiparametric quantitative cardiac magnetic resonance imaging [RESOURCE 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 - August 16, 2019 Category: Biomedical Science Authors: Baxan, N., Papanikolaou, A., Salles-Crawley, I., Lota, A., Chowdhury, R., Dubois, O., Branca, J., Hasham, M. G., Rosenthal, N., Prasad, S. K., Zhao, L., Harding, S. E., Sattler, S. Tags: RESOURCE ARTICLE Source Type: research

C9ORF72-related cellular pathology in skeletal myocytes derived from ALS-patient induced pluripotent stem cells [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 - August 16, 2019 Category: Biomedical Science Authors: Lynch, E., Semrad, T., Belsito, V. S., FitzGibbons, C., Reilly, M., Hayakawa, K., Suzuki, M. Tags: Stem Cells, Neurodegenerative disorders RESEARCH ARTICLE Source Type: research

First person - Martin Crivello and Marion Hogg [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. Martin Crivello and Marion Hogg are co-first authors on ‘Vascular regression precedes motor neuron loss in the FUS (1-359) ALS mouse model’, published in DMM. Martin, who is interested in molecular biology and neuroscience, will soon be joining Eurofins in a scientist position. Marion is a senior postdoc in the lab of Prof. Jochen Prehn at the Department of Physiology & Medical Physics and SFI...
Source: DMM Disease Models and Mechanisms - August 13, 2019 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

First person - Ling-shiang Chuang [FIRST PERSON]
ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms (DMM), helping early-career researchers promote themselves alongside their papers. Ling-shiang (Felix) Chuang is first author on ‘Zebrafish modeling of intestinal injury, bacterial exposures and medications defines epithelial in vivo responses relevant to human inflammatory bowel disease’, published in DMM. Ling-shiang is an instructor in the lab of Judy Cho at Icahn School of Medicine at Mount Sinai, New York, USA, investigating how to establish human genetic-driven perso...
Source: DMM Disease Models and Mechanisms - August 13, 2019 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

Vascular regression precedes motor neuron loss in the FUS (1-359) ALS mouse model [RESEARCH ARTICLE]
This article has an associated First Person interview with the joint first authors of the paper. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - August 13, 2019 Category: Biomedical Science Authors: Crivello, M., Hogg, M. C., Jirström, E., Halang, L., Woods, I., Rayner, M., Coughlan, K. S., Lewandowski, S. A., Prehn, J. H. M. Tags: Neurodegenerative disorders RESEARCH ARTICLE Source Type: research

The expanding spectrum of neurological disorders of phosphoinositide metabolism [REVIEW]
ABSTRACT Phosphoinositides (PIPs) are a ubiquitous group of seven low-abundance phospholipids that play a crucial role in defining localized membrane properties and that regulate myriad cellular processes, including cytoskeletal remodeling, cell signaling cascades, ion channel activity and membrane traffic. PIP homeostasis is tightly regulated by numerous inositol kinases and phosphatases, which phosphorylate and dephosphorylate distinct PIP species. The importance of these phospholipids, and of the enzymes that regulate them, is increasingly being recognized, with the identification of human neurological disorders that ar...
Source: DMM Disease Models and Mechanisms - August 13, 2019 Category: Biomedical Science Authors: Volpatti, J. R., Al-Maawali, A., Smith, L., Al-Hashim, A., Brill, J. A., Dowling, J. J. Tags: REVIEW Source Type: research

Zebrafish modeling of intestinal injury, bacterial exposures and medications defines epithelial in vivo responses relevant to human inflammatory bowel disease [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 - August 13, 2019 Category: Biomedical Science Authors: Chuang, L.-s., Morrison, J., Hsu, N.-y., Labrias, P. R., Nayar, S., Chen, E., Villaverde, N., Facey, J. A., Boschetti, G., Giri, M., Castillo-Martin, M., Thin, T. H., Sharma, Y., Chu, J., Cho, J. H. Tags: Zebrafish as a Disease Model RESEARCH ARTICLE Source Type: research

Mild maternal hyperglycemia in INSC93S transgenic pigs causes impaired glucose tolerance and metabolic alterations in neonatal offspring [RESEARCH ARTICLE]
ABSTRACT Alongside the obesity epidemic, the prevalence of maternal diabetes is rising worldwide, and adverse effects on fetal development and metabolic disturbances in the offspring's later life have been described. To clarify whether metabolic programming effects are due to mild maternal hyperglycemia without confounding obesity, we investigated wild-type offspring of INSC93S transgenic pigs, which are a novel genetically modified large-animal model expressing mutant insulin (INS) C93S in pancreatic β-cells. This mutation results in impaired glucose tolerance, mild fasting hyperglycemia and insulin resistance during...
Source: DMM Disease Models and Mechanisms - August 12, 2019 Category: Biomedical Science Authors: Renner, S., Martins, A. S., Streckel, E., Braun-Reichhart, C., Backman, M., Prehn, C., Klymiuk, N., Bähr, A., Blutke, A., Landbrecht-Schessl, C., Wünsch, A., Kessler, B., Kurome, M., Hinrichs, A., Koopmans, S.-J., Krebs, S., Kemter, E., Ra Tags: Metabolic Disorders RESEARCH ARTICLE Source Type: research

Next-generation RNA sequencing of FFPE subsections reveals highly conserved stromal reprogramming between canine and human mammary carcinoma [RESEARCH ARTICLE]
In conclusion, we provide a proof-of-principle to analyse specific subsections of FFPE tissue by RNAseq, and compare stromal gene expression between human and canine mCA to reveal molecular drivers in CAS supporting tumour growth and malignancy. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - August 8, 2019 Category: Biomedical Science Authors: Amini, P., Nassiri, S., Ettlin, J., Malbon, A., Markkanen, E. Tags: Cancer RESEARCH ARTICLE Source Type: research

The zebrafish subcortical social brain as a model for studying social behavior disorders [REVIEW]
ABSTRACT Social behaviors are essential for the survival and reproduction of social species. Many, if not most, neuropsychiatric disorders in humans are either associated with underlying social deficits or are accompanied by social dysfunctions. Traditionally, rodent models have been used to model these behavioral impairments. However, rodent assays are often difficult to scale up and adapt to high-throughput formats, which severely limits their use for systems-level science. In recent years, an increasing number of studies have used zebrafish (Danio rerio) as a model system to study social behavior. These studies have dem...
Source: DMM Disease Models and Mechanisms - August 6, 2019 Category: Biomedical Science Authors: Geng, Y., Peterson, R. T. Tags: Zebrafish as a Disease Model REVIEW Source Type: research

First person - Francesco Chiani and Tiziana Orsini [FIRST PERSON]
ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms (DMM), helping early-career researchers promote themselves alongside their papers. Francesco Chiani and Tiziana Orsini are co-first authors on ‘Functional loss of Ccdc151 leads to hydrocephalus in a mouse model of primary ciliary dyskinesia’, published in DMM. Francesco is a researcher (PhD) in the lab of Fabio Mammano (Italian IMPC/INFRANFRONTIER delegate) at the Institute of Biochemistry and Cell Biology – Italian National Research Council, Monterotondo, Rome, Ital...
Source: DMM Disease Models and Mechanisms - August 2, 2019 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

Functional loss of Ccdc151 leads to hydrocephalus in a mouse model of primary ciliary dyskinesia [RESEARCH ARTICLE]
This article has an associated First Person interview with the joint first authors of the paper. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - August 2, 2019 Category: Biomedical Science Authors: Chiani, F., Orsini, T., Gambadoro, A., Pasquini, M., Putti, S., Cirilli, M., Ermakova, O., Tocchini-Valentini, G. P. Tags: RESEARCH ARTICLE Source Type: research

The latest from the preLights community - July 2019 [PREPRINT HIGHLIGHTS]
(Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - August 2, 2019 Category: Biomedical Science Tags: PREPRINT HIGHLIGHTS Source Type: research

Disease modelling in human organoids [AT A GLANCE]
This article and accompanying poster highlight the currently available methods, particularly those aimed at modelling human biology, and provide an overview of their capabilities and limitations. We also speculate on possible future technological advances that have the potential for great strides in both disease modelling and future regenerative strategies. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - July 29, 2019 Category: Biomedical Science Authors: Lancaster, M. A., Huch, M. Tags: Organoids AT A GLANCE Source Type: research

First person - Marie Rodinova [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. Marie Vanisova (née Rodinova) is first author on ‘Skeletal muscle in an early manifest transgenic minipig model of Huntington's disease revealed deterioration of mitochondrial bioenergetics and ultrastructure impairment’, published in DMM. Marie is a PhD student in the lab of Hana Hansikova in the Department of Paediatrics and Adolescent Medicine, Charles University and General University H...
Source: DMM Disease Models and Mechanisms - July 26, 2019 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

Deterioration of mitochondrial bioenergetics and ultrastructure impairment in skeletal muscle of a transgenic minipig model in the early stages of Huntington's disease [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 - July 26, 2019 Category: Biomedical Science Authors: Rodinova, M., Krizova, J., Stufkova, H., Bohuslavova, B., Askeland, G., Dosoudilova, Z., Juhas, S., Juhasova, J., Ellederova, Z., Zeman, J., Eide, L., Motlik, J., Hansikova, H. Tags: Rare diseases RESEARCH ARTICLE Source Type: research

Modelling the MYC-driven normal-to-tumour switch in breast cancer [RESEARCH ARTICLE]
ABSTRACT The potent MYC oncoprotein is deregulated in many human cancers, including breast carcinoma, and is associated with aggressive disease. To understand the mechanisms and vulnerabilities of MYC-driven breast cancer, we have generated an in vivo model that mimics human disease in response to MYC deregulation. MCF10A cells ectopically expressing a common breast cancer mutation in the phosphoinositide 3 kinase pathway (PIK3CAH1047R) led to the development of organised acinar structures in mice. Expressing both PIK3CAH1047R and deregulated MYC led to the development of invasive ductal carcinoma. Therefore, the deregulat...
Source: DMM Disease Models and Mechanisms - July 26, 2019 Category: Biomedical Science Authors: Lourenco, C., Kalkat, M., Houlahan, K. E., De Melo, J., Longo, J., Done, S. J., Boutros, P. C., Penn, L. Z. Tags: Cancer RESEARCH ARTICLE Source Type: research

Genome-wide analysis of androgen receptor binding and transcriptomic analysis in mesenchymal subsets during prostate development [RESOURCE ARTICLE]
We examined AR function at single-cell resolution using single-cell RNA sequencing (scRNA-seq) in male and female mesenchyme. Surprisingly, both AR and target genes were distributed throughout cell subsets, with few positive cells within each subset. AR binding was weakly correlated with target gene expression. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - July 25, 2019 Category: Biomedical Science Authors: Nash, C., Boufaied, N., Badescu, D., Wang, Y. C., Paliouras, M., Trifiro, M., Ragoussis, I., Thomson, A. A. Tags: RESOURCE ARTICLE Source Type: research

Photoacoustic imaging as a tool to probe the tumour microenvironment [REVIEW]
ABSTRACT The tumour microenvironment (TME) is a complex cellular ecosystem subjected to chemical and physical signals that play a role in shaping tumour heterogeneity, invasion and metastasis. Studying the roles of the TME in cancer progression would strongly benefit from non-invasive visualisation of the tumour as a whole organ in vivo, both preclinically in mouse models of the disease, as well as in patient tumours. Although imaging techniques exist that can probe different facets of the TME, they face several limitations, including limited spatial resolution, extended scan times and poor specificity from confounding sig...
Source: DMM Disease Models and Mechanisms - July 16, 2019 Category: Biomedical Science Authors: Brown, E., Brunker, J., Bohndiek, S. E. Tags: Cancer REVIEW Source Type: research

Active receptor tyrosine kinases, but not Brachyury, are sufficient to trigger chordoma in zebrafish [RESEARCH ARTICLE]
ABSTRACT The aberrant activation of developmental processes triggers diverse cancer types. Chordoma is a rare, aggressive tumor arising from transformed notochord remnants. Several potentially oncogenic factors have been found to be deregulated in chordoma, yet causation remains uncertain. In particular, sustained expression of TBXT – encoding the notochord regulator protein brachyury – is hypothesized as a key driver of chordoma, yet experimental evidence is absent. Here, we employ a zebrafish chordoma model to identify the notochord-transforming potential of implicated genes in vivo. We find that Brachyury, i...
Source: DMM Disease Models and Mechanisms - July 16, 2019 Category: Biomedical Science Authors: D'Agati, G., Cabello, E. M., Frontzek, K., Rushing, E. J., Klemm, R., Robinson, M. D., White, R. M., Mosimann, C., Burger, A. Tags: Cancer, Rare diseases, Zebrafish as a Disease Model RESEARCH ARTICLE Source Type: research

Insulin receptor substrate 2 (IRS2) deficiency delays liver fibrosis associated with cholestatic injury [RESEARCH ARTICLE]
ABSTRACT Insulin receptor substrate 2 (IRS2) is a key downstream mediator of insulin and insulin-like growth factor 1 (IGF1) signalling pathways and plays a major role in liver metabolism. The aim of this study was to investigate whether IRS2 had an impact on the hepatic fibrotic process associated with cholestatic injury. Bile duct ligation (BDL) was performed in wild-type (WT) and Irs2-deficient (IRS2KO) female mice. Histological and biochemical analyses, together with fibrogenic and inflammatory responses were evaluated in livers from mice at 3, 7 and 28 days following BDL. We also explored whether activation of hu...
Source: DMM Disease Models and Mechanisms - July 16, 2019 Category: Biomedical Science Authors: Villar-Lorenzo, A., Rada, P., Rey, E., Maranon, P., Arroba, A. I., Santamaria, B., Saiz, J., Ruperez, F. J., Barbas, C., Garcia-Monzon, C., Valverde, A. M., Gonzalez-Rodriguez, A. Tags: RESEARCH ARTICLE Source Type: research

Morphological and functional correlates of vestibular synaptic deafferentation and repair in a mouse model of acute-onset vertigo [RESEARCH ARTICLE]
ABSTRACT Damage to cochlear primary afferent synapses has been shown to be a key factor in various auditory pathologies. Similarly, the selective lesioning of primary vestibular synapses might be an underlying cause of peripheral vestibulopathies that cause vertigo and dizziness, for which the pathophysiology is currently unknown. To thoroughly address this possibility, we selectively damaged the synaptic contacts between hair cells and primary vestibular neurons in mice through the transtympanic administration of a glutamate receptor agonist. Using a combination of histological and functional approaches, we demonstrated f...
Source: DMM Disease Models and Mechanisms - July 15, 2019 Category: Biomedical Science Authors: Cassel, R., Bordiga, P., Carcaud, J., Simon, F., Beraneck, M., Le Gall, A., Benoit, A., Bouet, V., Philoxene, B., Besnard, S., Watabe, I., Pericat, D., Hautefort, C., Assie, A., Tonetto, A., Dyhrfjeld-Johnsen, J., Llorens, J., Tighilet, B., Chabbert, C. Tags: RESEARCH ARTICLE Source Type: research

Conserved properties of genetic architecture of renal and fat transcriptomes in rat models of insulin resistance [RESEARCH ARTICLE]
ABSTRACT To define renal molecular mechanisms that are affected by permanent hyperglycaemia and might promote phenotypes relevant to diabetic nephropathy, we carried out linkage analysis of genome-wide gene transcription in the kidneys of F2 offspring from the Goto-Kakizaki (GK) rat model of type 2 diabetes and normoglycaemic Brown Norway (BN) rats. We mapped 2526 statistically significant expression quantitative trait loci (eQTLs) in the cross. More than 40% of eQTLs mapped in the close vicinity of the linked transcripts, underlying possible cis-regulatory mechanisms of gene expression. We identified eQTL hotspots on chro...
Source: DMM Disease Models and Mechanisms - July 15, 2019 Category: Biomedical Science Authors: Otto, G. W., Kaisaki, P. J., Brial, F., Le Lay, A., Cazier, J.-B., Mott, R., Gauguier, D. Tags: Metabolic Disorders, Rat as a Disease Model RESEARCH ARTICLE Source Type: research

First person - Christiaan Veerman [FIRST PERSON]
ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms (DMM), helping early-career researchers promote themselves alongside their papers. Christiaan Veerman is first author on ‘Genetic variation in GNB5 causes bradycardia by augmenting the cholinergic response via increased acetylcholine-activated potassium current (IK,Ach)’, published in DMM. Christiaan is a resident in cardiology in the lab of Prof. Bezzina at University of Amsterdam, The Netherlands, investigating pathophysiological mechanisms of inheritable cardiac arrhyth...
Source: DMM Disease Models and Mechanisms - July 9, 2019 Category: Biomedical Science Tags: FIRST PERSON Source Type: research

Development of mouse models of angiosarcoma driven by p53 [RESEARCH ARTICLE]
ABSTRACT Angiosarcomas are a rare group of tumours which have poor prognosis and limited treatment options. The development of new therapies has been hampered by a lack of good preclinical models. Here, we describe the development of an autochthonous mouse model of angiosarcoma driven by loss of p53 in VE-cadherin-expressing endothelial cells. Using Cdh5-Cre to drive recombination in adult endothelial cells, mice developed angiosarcomas with 100% penetrance upon homozygous deletion of Trp53 with a median lifespan of 325 days. In contrast, expression of the R172H mutant p53 resulted in formation of thymic lymphomas wit...
Source: DMM Disease Models and Mechanisms - July 9, 2019 Category: Biomedical Science Authors: Salter, D. M., Griffin, M., Muir, M., Teo, K., Culley, J., Smith, J. R., Gomez-Cuadrado, L., Matchett, K., Sims, A. H., Hayward, L., Henderson, N. C., Brunton, V. G. Tags: Cancer, Rare diseases RESEARCH ARTICLE Source Type: research

Standardised imaging pipeline for phenotyping mouse laterality defects and associated heart malformations, at multiple scales and multiple stages [RESOURCE ARTICLE]
ABSTRACT Laterality defects are developmental disorders resulting from aberrant left/right patterning. In the most severe cases, such as in heterotaxy, they are associated with complex malformations of the heart. Advances in understanding the underlying physiopathological mechanisms have been hindered by the lack of a standardised and exhaustive procedure in mouse models for phenotyping left/right asymmetries of all visceral organs. Here, we have developed a multimodality imaging pipeline, which combines non-invasive micro-ultrasound imaging, micro-computed tomography (micro-CT) and high-resolution episcopic microscopy (HR...
Source: DMM Disease Models and Mechanisms - July 9, 2019 Category: Biomedical Science Authors: Desgrange, A., Lokmer, J., Marchiol, C., Houyel, L., Meilhac, S. M. Tags: RESOURCE ARTICLE Source Type: research

Genetic variation in GNB5 causes bradycardia by augmenting the cholinergic response via increased acetylcholine-activated potassium current (IK,ACh) [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 - July 9, 2019 Category: Biomedical Science Authors: Veerman, C. C., Mengarelli, I., Koopman, C. D., Wilders, R., van Amersfoorth, S. C., Bakker, D., Wolswinkel, R., Hababa, M., de Boer, T. P., Guan, K., Milnes, J., Lodder, E. M., Bakkers, J., Verkerk, A. O., Bezzina, C. R. Tags: Stem Cells, Zebrafish as a Disease Model RESEARCH ARTICLE Source Type: research

The MMTV-Wnt1 murine model produces two phenotypically distinct subtypes of mammary tumors with unique therapeutic responses to an EGFR inhibitor [RESEARCH ARTICLE]
This study definitively shows that the MMTV-Wnt1 mouse model produces two phenotypically distinct subtypes of mammary tumors that differ in multiple biological aspects including sensitivity to an EGFR inhibitor. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - July 5, 2019 Category: Biomedical Science Authors: Pfefferle, A. D., Darr, D. B., Calhoun, B. C., Mott, K. R., Rosen, J. M., Perou, C. M. Tags: Cancer RESEARCH ARTICLE Source Type: research

RDH10 function is necessary for spontaneous fetal mouth movement that facilitates palate shelf elevation [RESEARCH ARTICLE]
This study extends the range of anomalies directly demonstrated to have fetal mouth movement defects correlated with cleft palate. Here, we show that mouse embryos deficient in retinoic acid (RA) have mispatterned pharyngeal nerves and skeletal elements that block spontaneous fetal mouth movement in utero. Using X-ray microtomography, in utero ultrasound video, ex vivo culture and tissue staining, we demonstrate that proper retinoid signaling and pharyngeal patterning are crucial for the fetal mouth movement needed for palate formation. Embryos with deficient retinoid signaling were generated by stage-specific inactivation...
Source: DMM Disease Models and Mechanisms - July 3, 2019 Category: Biomedical Science Authors: Friedl, R. M., Raja, S., Metzler, M. A., Patel, N. D., Brittian, K. R., Jones, S. P., Sandell, L. L. Tags: RESEARCH ARTICLE Source Type: research