A novel mouse model of Duchenne muscular dystrophy carrying a multi-exonic Dmd deletion exhibits progressive muscular dystrophy and early-onset cardiomyopathy [RESEARCH ARTICLE]
ABSTRACT
Duchenne muscular dystrophy (DMD) is a life-threatening neuromuscular disease caused by the lack of dystrophin, resulting in progressive muscle wasting and locomotor dysfunctions. By adulthood, almost all patients also develop cardiomyopathy, which is the primary cause of death in DMD. Although there has been extensive effort in creating animal models to study treatment strategies for DMD, most fail to recapitulate the complete skeletal and cardiac disease manifestations that are presented in affected patients. Here, we generated a mouse model mirroring a patient deletion mutation of exons 52-54 (Dmd 52-54). The D...
Source: DMM Disease Models and Mechanisms - September 20, 2020 Category: Biomedical Science Authors: Wong, T. W. Y., Ahmed, A., Yang, G., Maino, E., Steiman, S., Hyatt, E., Chan, P., Lindsay, K., Wong, N., Golebiowski, D., Schneider, J., Delgado-Olguin, P., Ivakine, E. A., Cohn, R. D. Tags: Neuromuscular RESEARCH ARTICLE Source Type: research
Rabphilin involvement in filtration and molecular uptake in Drosophila nephrocytes suggests a similar role in human podocytes [RESEARCH ARTICLE]
ABSTRACT
Drosophila nephrocytes share functional, structural and molecular similarities with human podocytes. It is known that podocytes express the rabphilin 3A (RPH3A)-RAB3A complex, and its expression is altered in mouse and human proteinuric disease. Furthermore, we previously identified a polymorphism that suggested a role for RPH3A protein in the development of urinary albumin excretion. As endocytosis and vesicle trafficking are fundamental pathways for nephrocytes, the objective of this study was to assess the role of the RPH3A orthologue in Drosophila, Rabphilin (Rph), in the structure and function of nephrocytes....
Source: DMM Disease Models and Mechanisms - September 20, 2020 Category: Biomedical Science Authors: Selma-Soriano, E., Llamusi, B., Fernandez-Costa, J. M., Ozimski, L. L., Artero, R., Redon, J. Tags: Drosophila as a Disease Model RESEARCH ARTICLE Source Type: research
Circulating exosomal microRNAs as potential biomarkers of hepatic injury and inflammation in a murine model of glycogen storage disease type 1a [RESEARCH ARTICLE]
ABSTRACT
Most patients affected by glycogen storage disease type 1a (GSD1a), an inherited metabolic disorder caused by mutations in the enzyme glucose-6-phosphatase-α (G6Pase-α), develop renal and liver complications, including the development of hepatocellular adenoma/carcinoma. The purpose of this study was to identify potential biomarkers of the pathophysiology of the GSD1a-affected liver. To this end, we used the plasma exosomes of a murine model of GSD1a, the LS-G6pc–/– mouse, to uncover the modulation in microRNA expression associated with the disease. The microRNAs differentially expressed be...
Source: DMM Disease Models and Mechanisms - September 17, 2020 Category: Biomedical Science Authors: Resaz, R., Cangelosi, D., Morini, M., Segalerba, D., Mastracci, L., Grillo, F., Bosco, M. C., Bottino, C., Colombo, I., Eva, A. Tags: Rare diseases RESEARCH ARTICLE Source Type: research
Neonatal and infant immunity for tuberculosis vaccine development: importance of age-matched animal models [REVIEW]
ABSTRACT
Neonatal and infant immunity differs from that of adults in both the innate and adaptive arms, which are critical contributors to immune-mediated clearance of infection and memory responses elicited during vaccination. The tuberculosis (TB) research community has openly admitted to a vacuum of knowledge about neonatal and infant immune responses to Mycobacterium tuberculosis (Mtb) infection, especially in the functional and phenotypic attributes of memory T cell responses elicited by the only available vaccine for TB, the Bacillus Calmette–Guérin (BCG) vaccine. Although BCG vaccination has variable ef...
Source: DMM Disease Models and Mechanisms - September 14, 2020 Category: Biomedical Science Authors: Ramos, L., Lunney, J. K., Gonzalez-Juarrero, M. Tags: REVIEW Source Type: research
Cell and animal models of SARS-CoV-2 pathogenesis and immunity [SPECIAL ARTICLE]
ABSTRACT
The spread of the novel virus SARS coronavirus 2 (SARS-CoV-2) was explosive, with cases first identified in December 2019, and >22 million people infected and >775,000 deaths as of August 2020. SARS-CoV-2 can cause severe respiratory disease in humans leading to coronavirus disease 2019 (COVID-19). The development of effective clinical interventions, such as antivirals and vaccines that can limit or even prevent the burden and spread of SARS-CoV-2, is a global health priority. Testing of leading antivirals, monoclonal antibody therapies and vaccines against SARS-CoV-2 will require robust animal and cell mode...
Source: DMM Disease Models and Mechanisms - August 31, 2020 Category: Biomedical Science Authors: Leist, S. R., Schäfer, A., Martinez, D. R. Tags: SPECIAL ARTICLE Source Type: research
First person - Pratibha Singh [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. Pratibha Singh is first author on ‘Maltodextrin-induced intestinal injury in a neonatal mouse model’, published in DMM. Pratibha is a postdoctoral research fellow in the lab of Dr Camilia R. Martin at Harvard Medical School, Boston, MA, USA, investigating nutrient-driven immunomodulation in neonatal health and disease. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - August 26, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research
First person - Hui-Ying Tsai and Shih-Cheng Wu [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. Hui-Ying Tsai and Shih-Cheng Wu are co-first authors on ‘Loss of the Drosophila branched-chain α-ketoacid dehydrogenase complex results in neuronal dysfunction’, published in DMM. Hui-Ying is a research assistant in the lab of Chun-Hong Chen at National Health Research Institutes, Zhunan, Taiwan. Her research interest is modeling the human neurological disease maple syrup urine disease in Dr...
Source: DMM Disease Models and Mechanisms - August 26, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research
Sex-dependent effect of APOE on Alzheimer's disease and other age-related neurodegenerative disorders [REVIEW]
ABSTRACT
The importance of apolipoprotein E (APOE) in late-onset Alzheimer's disease (LOAD) has been firmly established, but the mechanisms through which it exerts its pathogenic effects remain elusive. In addition, the sex-dependent effects of APOE on LOAD risk and endophenotypes have yet to be explained. In this Review, we revisit the different aspects of APOE involvement in neurodegeneration and neurological diseases, with particular attention to sex differences in the contribution of APOE to LOAD susceptibility. We discuss the role of APOE in a broader range of age-related neurodegenerative diseases, and summarize the ...
Source: DMM Disease Models and Mechanisms - August 26, 2020 Category: Biomedical Science Authors: Gamache, J., Yun, Y., Chiba-Falek, O. Tags: Neurodegenerative disorders REVIEW Source Type: research
A regulated NMD mouse model supports NMD inhibition as a viable therapeutic option to treat genetic diseases [RESEARCH ARTICLE]
ABSTRACT
Nonsense-mediated mRNA decay (NMD) targets mRNAs that contain a premature termination codon (PTC) for degradation, preventing their translation. By altering the expression of PTC-containing mRNAs, NMD modulates the inheritance pattern and severity of genetic diseases. NMD also limits the efficiency of suppressing translation termination at PTCs, an emerging therapeutic approach to treat genetic diseases caused by in-frame PTCs (nonsense mutations). Inhibiting NMD may help rescue partial levels of protein expression. However, it is unclear whether long-term, global NMD attenuation is safe. We hypothesize that a deg...
Source: DMM Disease Models and Mechanisms - August 26, 2020 Category: Biomedical Science Authors: Echols, J., Siddiqui, A., Dai, Y., Havasi, V., Sun, R., Kaczmarczyk, A., Keeling, K. M. Tags: RESEARCH ARTICLE Source Type: research
Maltodextrin-induced intestinal injury in a neonatal mouse model [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 26, 2020 Category: Biomedical Science Authors: Singh, P., Sanchez-Fernandez, L. L., Ramiro-Cortijo, D., Ochoa-Allemant, P., Perides, G., Liu, Y., Medina-Morales, E., Yakah, W., Freedman, S. D., Martin, C. R. Tags: RESEARCH ARTICLE Source Type: research
Loss of the Drosophila branched-chain {alpha}-ketoacid dehydrogenase complex results in neuronal dysfunction [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 26, 2020 Category: Biomedical Science Authors: Tsai, H.-Y., Wu, S.-C., Li, J.-C., Chen, Y.-M., Chan, C.-C., Chen, C.-H. Tags: Drosophila as a Disease Model RESEARCH ARTICLE Source Type: research
Generation and characterization of an Il2rg knockout Syrian hamster model for XSCID and HAdV-C6 infection in immunocompromised patients [RESEARCH ARTICLE]
ABSTRACT
Model animals are indispensable for the study of human diseases, and in general, of complex biological processes. The Syrian hamster is an important model animal for infectious diseases, behavioral science and metabolic science, for which more experimental tools are becoming available. Here, we describe the generation and characterization of an interleukin-2 receptor subunit gamma (Il2rg) knockout (KO) Syrian hamster strain. In humans, mutations in IL2RG can result in a total failure of T and natural killer (NK) lymphocyte development and nonfunctional B lymphocytes (X-linked severe combined immunodeficiency; XSCI...
Source: DMM Disease Models and Mechanisms - August 26, 2020 Category: Biomedical Science Authors: Li, R., Ying, B., Liu, Y., Spencer, J. F., Miao, J., Tollefson, A. E., Brien, J. D., Wang, Y., Wold, W. S. M., Wang, Z., Toth, K. Tags: RESEARCH ARTICLE Source Type: research
suz12 inactivation in p53- and nf1-deficient zebrafish accelerates the onset of malignant peripheral nerve sheath tumors and expands the spectrum of tumor types [RESEARCH ARTICLE]
ABSTRACT
Polycomb repressive complex 2 (PRC2) is an epigenetic regulator of gene expression that possesses histone methyltransferase activity. PRC2 trimethylates lysine 27 of histone H3 proteins (H3K27me3) as a chromatin modification associated with repressed transcription of genes frequently involved in cell proliferation or self-renewal. Loss-of-function mutations in the PRC2 core subunit SUZ12 have been identified in a variety of tumors, including malignant peripheral nerve sheath tumors (MPNSTs). To determine the consequences of SUZ12 loss in the pathogenesis of MPNST and other cancers, we used CRISPR-Cas9 to disrupt t...
Source: DMM Disease Models and Mechanisms - August 26, 2020 Category: Biomedical Science Authors: Oppel, F., Ki, D. H., Zimmerman, M. W., Ross, K. N., Tao, T., Shi, H., He, S., Aster, J. C., Look, A. T. Tags: Cancer, Zebrafish as a Disease Model RESEARCH ARTICLE Source Type: research
Integrating fish models in tuberculosis vaccine development [REVIEW]
ABSTRACT
Tuberculosis is a chronic infection by Mycobacterium tuberculosis that results in over 1.5 million deaths worldwide each year. Currently, there is only one vaccine against tuberculosis, the Bacillus Calmette–Guérin (BCG) vaccine. Despite widespread vaccination programmes, over 10 million new M. tuberculosis infections are diagnosed yearly, with almost half a million cases caused by antibiotic-resistant strains. Novel vaccination strategies concentrate mainly on replacing BCG or boosting its efficacy and depend on animal models that accurately recapitulate the human disease. However, efforts to produce...
Source: DMM Disease Models and Mechanisms - August 22, 2020 Category: Biomedical Science Authors: Saralahti, A. K., Uusi-Mäkelä, M. I. E., Niskanen, M. T., Rämet, M. Tags: Model Systems in Drug Discovery, Zebrafish as a Disease Model REVIEW Source Type: research
First person - Mohd. Salman [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. Mohd. Salman is first author on ‘Nrf2/HO-1 mediates the neuroprotective effects of pramipexole by attenuating oxidative damage and mitochondrial perturbation after traumatic brain injury in rats’, published in DMM. Mohd. is a PhD student in the lab of Prof. Suhel Parvez at Jamia Hamdard, New Delhi, India, investigating the cellular and molecular mechanisms involved in traumatic brain injury, ische...
Source: DMM Disease Models and Mechanisms - August 18, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research
