Sensory neuron cultures derived from adult db/db mice as a simplified model to study type-2 diabetes-associated axonal regeneration defects [RESEARCH ARTICLE]
ABSTRACT
Diabetic neuropathy (DN) is an early common complication of diabetes mellitus (DM), leading to chronic pain, sensory loss and muscle atrophy. Owing to its multifactorial etiology, neuron in vitro cultures have been proposed as simplified systems for DN studies. However, the most used models currently available do not recreate the chronic and systemic damage suffered by peripheral neurons of type-2 DM (T2DM) individuals. Here, we cultured neurons derived from dorsal root ganglia from 6-month-old diabetic db/db-mice, and evaluated their morphology by the Sholl method as an easy-to-analyze readout of neuronal functio...
Source: DMM Disease Models and Mechanisms - January 22, 2021 Category: Biomedical Science Authors: De Gregorio, C., Ezquer, F. Tags: Metabolic Disorders RESEARCH ARTICLE Source Type: research
Head-to-head study of oxelumab and adalimumab in a mouse model of ulcerative colitis based on NOD/Scid IL2R{gamma}null mice reconstituted with human peripheral blood mononuclear cells [RESEARCH ARTICLE]
This study's aim was to demonstrate that the combination of patient immune profiling and testing in a humanized mouse model of ulcerative colitis (UC) might lead to patient stratification for treatment with oxelumab. First, immunological profiles of UC patients and non-UC donors were analyzed for CD4+ T cells expressing OX40 (CD134; also known as TNFRSF4) and CD14+ monocytes expressing OX40L (CD252; also known as TNFSF4) by flow cytometric analysis. A significant difference was observed between the groups for CD14+ OX40L+ (UC: n=11, 85.44±21.17, mean±s.d.; non-UC: n=5, 30.7±34.92; P=0.02), whereas no s...
Source: DMM Disease Models and Mechanisms - January 21, 2021 Category: Biomedical Science Authors: Jodeleit, H., Winkelmann, P., Caesar, J., Sterz, S., Holdt, L. M., Beigel, F., Stallhofer, J., Breiteneicher, S., Bartnik, E., Leeuw, T., Siebeck, M., Gropp, R. Tags: Model Systems in Drug Discovery RESEARCH ARTICLE Source Type: research
Heterogeneity in clone dynamics within and adjacent to intestinal tumours identified by Dre-mediated lineage tracing [RESEARCH ARTICLE]
ABSTRACT
Somatic models of tissue pathology commonly use induction of gene-specific mutations in mice mediated by spatiotemporal regulation of Cre recombinase. Subsequent investigation of the onset and development of disease can be limited by the inability to track changing cellular behaviours over time. Here, a lineage-tracing approach based on ligand-dependent activation of Dre recombinase that can be employed independently of Cre is described. The clonal biology of the intestinal epithelium following Cre-mediated stabilisation of β-catenin reveals that, within tumours, many new clones rapidly become extinct. Surviv...
Source: DMM Disease Models and Mechanisms - January 15, 2021 Category: Biomedical Science Authors: Thorsen, A.-S., Khamis, D., Kemp, R., Colombe, M., Lourenco, F. C., Morrissey, E., Winton, D. Tags: Cancer RESEARCH ARTICLE Source Type: research
Correction: A novel hypomorphic allele of Spag17 causes primary ciliary dyskinesia phenotypes in mice [CORRECTION]
(Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - January 11, 2021 Category: Biomedical Science Authors: Abdelhamed, Z., Lukacs, M., Cindric, S., Ali, S., Omran, H., Stottmann, R. W. Tags: Developmental Disorders CORRECTION Source Type: research
Regulation of murine copper homeostasis by members of the COMMD protein family [RESEARCH ARTICLE]
In this study, we examined copper homeostasis in enterocyte-specific and hepatocyte-specific COMMD gene-deficient mice. We found that, in contrast to effects in cell lines in culture, COMMD protein deficiency induced minimal changes in ATP7A in enterocytes and did not lead to altered copper levels under low- or high-copper diets, suggesting that regulation of ATP7A in enterocytes is not of physiological consequence. By contrast, deficiency of any of three COMMD genes (Commd1, Commd6 or Commd9) resulted in hepatic copper accumulation under high-copper diets. We found that each of these deficiencies caused destabilization of...
Source: DMM Disease Models and Mechanisms - January 7, 2021 Category: Biomedical Science Authors: Singla, A., Chen, Q., Suzuki, K., Song, J., Fedoseienko, A., Wijers, M., Lopez, A., Billadeau, D. D., van de Sluis, B., Burstein, E. Tags: RESEARCH ARTICLE Source Type: research
Impaired muscle morphology in a Drosophila model of myosin storage myopathy was suppressed by overexpression of an E3 ubiquitin ligase [RESEARCH ARTICLE]
This study shows that a higher expression level of the mutated allele is concomitant with severe impairment of muscle function and progressively disrupted muscle morphology. The impaired muscle morphology associated with the mutant allele was suppressed by expression of Thin (herein referred to as Abba), an E3 ubiquitin ligase. This Drosophila model recapitulates pathological features seen in myopathy patients with the R1845W mutation and severe ultrastructural abnormalities, including extensive loss of thick filaments with selective A-band loss, and preservation of I-band and Z-disks were observed in indirect flight muscl...
Source: DMM Disease Models and Mechanisms - December 29, 2020 Category: Biomedical Science Authors: Dahl-Halvarsson, M., Olive, M., Pokrzywa, M., Norum, M., Ejeskär, K., Tajsharghi, H. Tags: Neuromuscular, Drosophila as a Disease Model RESEARCH ARTICLE Source Type: research
First person - Kim Landry-Truchon and Nicolas Houde [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. Kim Landry-Truchon is first author on ‘Deletion of Yy1 in mouse lung epithelium unveils molecular mechanisms governing pleuropulmonary blastoma pathogenesis’, published in DMM. Kim is a research assistant in the lab of Lucie Jeannotte at Centre de recherche du CHU de Québec-Université Laval, Québec, Canada, investigating organ development and the regulatory networks involved. ...
Source: DMM Disease Models and Mechanisms - December 29, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research
First person - Lozan Sheriff and Reenam Kahn [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. Lozan Sheriff and Reenam Kahn are co-first authors on ‘Alcoholic hepatitis and metabolic disturbance in female mice: a more tractable model than Nrf2–/– animals’, published in DMM. Lozan is a postdoctoral research fellow in the lab of Dr Patricia Lalor and Reenam a PhD student in the lab of Prof. Phil Newsome. Both are at the Centre for Liver and Gastrointestinal Research, Institute of...
Source: DMM Disease Models and Mechanisms - December 29, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research
Impaired muscle morphology in a Drosophila model of myosin storage myopathy was supressed by overexpression of an E3 ubiquitin ligase [RESEARCH ARTICLE]
This study shows that a higher expression level of the mutated allele is concomitant with severe impairment of muscle function and progressively disrupted muscle morphology. The impaired muscle morphology associated with the mutant allele was suppressed by expression of Thin (herein referred to as Abba), an E3 ubiquitin ligase. This Drosophila model recapitulates pathological features seen in myopathy patients with the R1845W mutation and severe ultrastructural abnormalities, including extensive loss of thick filaments with selective A-band loss, and preservation of I-band and Z-disks were observed in indirect flight muscl...
Source: DMM Disease Models and Mechanisms - December 29, 2020 Category: Biomedical Science Authors: Dahl-Halvarsson, M., Olive, M., Pokrzywa, M., Norum, M., Ejeskär, K., Tajsharghi, H. Tags: RESEARCH ARTICLE Source Type: research
Of numbers and movement - understanding transcription factor pathogenesis by advanced microscopy [REVIEW]
ABSTRACT
Transcription factors (TFs) are life-sustaining and, therefore, the subject of intensive research. By regulating gene expression, TFs control a plethora of developmental and physiological processes, and their abnormal function commonly leads to various developmental defects and diseases in humans. Normal TF function often depends on gene dosage, which can be altered by copy-number variation or loss-of-function mutations. This explains why TF haploinsufficiency (HI) can lead to disease. Since aberrant TF numbers frequently result in pathogenic abnormalities of gene expression, quantitative analyses of TFs are a pri...
Source: DMM Disease Models and Mechanisms - December 29, 2020 Category: Biomedical Science Authors: Auer, J. M. T., Stoddart, J. J., Christodoulou, I., Lima, A., Skouloudaki, K., Hall, H. N., Vukojevic, V., Papadopoulos, D. K. Tags: REVIEW Source Type: research
Alcoholic hepatitis and metabolic disturbance in female mice: a more tractable model than Nrf2-/- animals [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 - December 29, 2020 Category: Biomedical Science Authors: Sheriff, L., Khan, R. S., Saborano, R., Wilkin, R., Luu, N.-T., Gunther, U. L., Hubscher, S. G., Newsome, P. N., Lalor, P. F. Tags: Model Systems in Drug Discovery RESEARCH ARTICLE Source Type: research
Deletion of Yy1 in mouse lung epithelium unveils molecular mechanisms governing pleuropulmonary blastoma pathogenesis [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 - December 29, 2020 Category: Biomedical Science Authors: Landry-Truchon, K., Houde, N., Lhuillier, M., Charron, L., Hadchouel, A., Delacourt, C., Foulkes, W. D., Galmiche-Rolland, L., Jeannotte, L. Tags: Cancer, Developmental Disorders RESEARCH ARTICLE Source Type: research
Predicting experimental success: a retrospective case-control study using the rat intraluminal thread model of stroke [RESEARCH ARTICLE]
ABSTRACT
The poor translational success rate of preclinical stroke research may partly be due to inaccurate modelling of the disease. We provide data on transient middle cerebral artery occlusion (tMCAO) experiments, including detailed intraoperative monitoring to elaborate predictors indicating experimental success (ischemia without occurrence of confounding pathologies). The tMCAO monitoring data (bilateral cerebral blood flow, CBF; heart rate, HR; and mean arterial pressure, MAP) of 16 animals with an ‘ideal’ outcome (MCA-ischemia), and 48 animals with additional or other pathologies (subdural haematoma or s...
Source: DMM Disease Models and Mechanisms - December 29, 2020 Category: Biomedical Science Authors: Liebenstund, L., Coburn, M., Fitzner, C., Willuweit, A., Langen, K.-J., Liu, J., Veldeman, M., Höllig, A. Tags: Rat as a Disease Model RESEARCH ARTICLE Source Type: research
Disease Models & Mechanisms announces a new Editor-in-Chief [EDITORIAL]
(Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - December 22, 2020 Category: Biomedical Science Authors: Vyas, P. Tags: EDITORIAL Source Type: research
Modulating the endoplasmic reticulum stress response attenuates neurodegeneration in a Caenorhabditis elegans model of spinal muscular atrophy [RESEARCH ARTICLE]
ABSTRACT
Spinal muscular atrophy (SMA) is a devastating autosomal recessive neuromuscular disease resulting in muscle atrophy and neurodegeneration, and is the leading genetic cause of infant death. SMA arises when there are homozygous deletion mutations in the human SMN1 gene, leading to a decrease in corresponding SMN1 protein. Although SMN1 is expressed across multiple tissue types, much of the previous research into SMA focused on the neuronal aspect of the disease, overlooking many of the potential non-neuronal aspects of the disease. Therefore, we sought to address this gap in knowledge by modeling SMA in the nematod...
Source: DMM Disease Models and Mechanisms - December 22, 2020 Category: Biomedical Science Authors: Doyle, J. J., Vrancx, C., Maios, C., Labarre, A., Patten, S. A., Parker, J. A. Tags: Neuromuscular, C. elegans RESEARCH ARTICLE Source Type: research
