Inactivation of Zeb1 in GRHL2-deficient mouse embryos rescues mid-gestation viability and secondary palate closure [RESEARCH ARTICLE]
ABSTRACT
Cleft lip and palate are common birth defects resulting from failure of the facial processes to fuse during development. The mammalian grainyhead-like (Grhl1-3) genes play key roles in a number of tissue fusion processes including neurulation, epidermal wound healing and eyelid fusion. One family member, Grhl2, is expressed in the epithelial lining of the first pharyngeal arch in mice at embryonic day (E)10.5, prompting analysis of the role of this factor in palatogenesis. Grhl2-null mice die at E11.5 with neural tube defects and a cleft face phenotype, precluding analysis of palatal fusion at a later stage of dev...
Source: DMM Disease Models and Mechanisms - March 24, 2020 Category: Biomedical Science Authors: Carpinelli, M. R., de Vries, M. E., Auden, A., Butt, T., Deng, Z., Partridge, D. D., Miles, L. B., Georgy, S. R., Haigh, J. J., Darido, C., Brabletz, S., Brabletz, T., Stemmler, M. P., Dworkin, S., Jane, S. M. Tags: RESEARCH ARTICLE Source Type: research
First person - Carina Lund [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. Carina Lund is first author on ‘Characterization of the human GnRH neuron developmental transcriptome using a GNRH1-TdTomato reporter line in human pluripotent stem cells’, published in DMM. Carina is a PhD student in the lab of Taneli Raivio at the University of Helsinki, Finland, investigating neuronal differentiation from human pluripotent stem cells. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - March 12, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research
First person - Jorge Rodriguez-Gil [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. Jorge Rodriguez-Gil is first author on ‘Genetic background modifies phenotypic severity and longevity in a mouse model of Niemann-Pick disease type C1’, published in DMM. Jorge is a postdoctoral fellow in the lab of William J. Pavan (National Human Genome Research Institute) and Frances M. Platt (University of Oxford) investigating the genetic architecture of Niemann-Pick disease type C. (So...
Source: DMM Disease Models and Mechanisms - March 12, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research
Genetic background modifies phenotypic severity and longevity in a mouse model of Niemann-Pick disease type C1 [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 - March 12, 2020 Category: Biomedical Science Authors: Rodriguez-Gil, J. L., Watkins-Chow, D. E., Baxter, L. L., Elliot, G., Harper, U. L., Wincovitch, S. M., Wedel, J. C., Incao, A. A., Huebecker, M., Boehm, F. J., Garver, W. S., Porter, F. D., Broman, K. W., Platt, F. M., Pavan, W. J. Tags: Neurodegenerative disorders, Rare diseases RESEARCH ARTICLE Source Type: research
Characterization of the human GnRH neuron developmental transcriptome using a GNRH1-TdTomato reporter line in human 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 - March 12, 2020 Category: Biomedical Science Authors: Lund, C., Yellapragada, V., Vuoristo, S., Balboa, D., Trova, S., Allet, C., Eskici, N., Pulli, K., Giacobini, P., Tuuri, T., Raivio, T. Tags: Stem Cells RESEARCH ARTICLE Source Type: research
The latest from the preLights community - March 2020 [PREPRINT HIGHLIGHTS]
(Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - March 10, 2020 Category: Biomedical Science Tags: PREPRINT HIGHLIGHTS Source Type: research
Six1 proteins with human branchio-oto-renal mutations differentially affect cranial gene expression and otic development [RESEARCH ARTICLE]
ABSTRACT
Single-nucleotide mutations in human SIX1 result in amino acid substitutions in either the protein-protein interaction domain or the homeodomain, and cause ~4% of branchio-otic (BOS) and branchio-oto-renal (BOR) cases. The phenotypic variation between patients with the same mutation, even within affected members of the same family, make it difficult to functionally distinguish between the different SIX1 mutations. We made four of the BOS/BOR substitutions in the Xenopus Six1 protein (V17E, R110W, W122R, Y129C), which is 100% identical to human in both the protein-protein interaction domain and the homeodomain, and...
Source: DMM Disease Models and Mechanisms - March 2, 2020 Category: Biomedical Science Authors: Shah, A. M., Krohn, P., Baxi, A. B., Tavares, A. L. P., Sullivan, C. H., Chillakuru, Y. R., Majumdar, H. D., Neilson, K. M., Moody, S. A. Tags: RESEARCH ARTICLE Source Type: research
Biomarkers for Duchenne muscular dystrophy: myonecrosis, inflammation and oxidative stress [REVIEW]
ABSTRACT
Duchenne muscular dystrophy (DMD) is a lethal, X-linked disease that causes severe loss of muscle mass and function in young children. Promising therapies for DMD are being developed, but the long lead times required when using clinical outcome measures are hindering progress. This progress would be facilitated by robust molecular biomarkers in biofluids, such as blood and urine, which could be used to monitor disease progression and severity, as well as to determine optimal drug dosing before a full clinical trial. Many candidate DMD biomarkers have been identified, but there have been few follow-up studies to va...
Source: DMM Disease Models and Mechanisms - March 1, 2020 Category: Biomedical Science Authors: Grounds, M. D., Terrill, J. R., Al-Mshhdani, B. A., Duong, M. N., Radley-Crabb, H. G., Arthur, P. G. Tags: REVIEW Source Type: research
Moving neuromuscular disorders research forward: from novel models to clinical studies [EDITORIAL]
ABSTRACT
Neuromuscular disorders (NMDs) encompass a diverse group of genetic diseases characterized by loss of muscle functionality. Despite extensive efforts to develop therapies, no curative treatment exists for any of the NMDs. For multiple disorders, however, therapeutic strategies are currently being tested in clinical settings, and the first successful treatments have now entered clinical practice (e.g. spinraza for spinal muscular atrophy). Successful clinical translation depends on the quality and translatability of preclinical findings and on the predictive value of the experimental models used in their initial de...
Source: DMM Disease Models and Mechanisms - February 24, 2020 Category: Biomedical Science Authors: van Putten, M., Hmeljak, J., Aartsma-Rus, A., Dowling, J. J. Tags: Neuromuscular EDITORIAL Source Type: research
Mouse models for muscular dystrophies: an overview [REVIEW]
ABSTRACT
Muscular dystrophies (MDs) encompass a wide variety of inherited disorders that are characterized by loss of muscle tissue associated with a progressive reduction in muscle function. With a cure lacking for MDs, preclinical developments of therapeutic approaches depend on well-characterized animal models that recapitulate the specific pathology in patients. The mouse is the most widely and extensively used model for MDs, and it has played a key role in our understanding of the molecular mechanisms underlying MD pathogenesis. This has enabled the development of therapeutic strategies. Owing to advancements in genet...
Source: DMM Disease Models and Mechanisms - February 20, 2020 Category: Biomedical Science Authors: van Putten, M., Lloyd, E. M., de Greef, J. C., Raz, V., Willmann, R., Grounds, M. D. Tags: Neuromuscular, Model Systems in Drug Discovery, Tools and Resources for Mouse Studies REVIEW Source Type: research
Improving translatability of preclinical studies for neuromuscular disorders: lessons from the TREAT-NMD Advisory Committee for Therapeutics (TACT) [REVIEW]
ABSTRACT
Clinical trials for rare neuromuscular diseases imply, among other investments, a high emotional burden for the whole disease community. Translation of data from preclinical studies to justify any clinical trial must be carefully pondered in order to minimize the risk of clinical trial withdrawal or failure. A rigorous distinction between proof-of-concept and preclinical efficacy studies using animal models is key to support the rationale of a clinical trial involving patients. This Review evaluates the experience accumulated by the TREAT-NMD Advisory Committee for Therapeutics, which provides detailed constructiv...
Source: DMM Disease Models and Mechanisms - February 6, 2020 Category: Biomedical Science Authors: Willmann, R., Lee, J., Turner, C., Nagaraju, K., Aartsma-Rus, A., Wells, D. J., Wagner, K. R., Csimma, C., Straub, V., Grounds, M. D., De Luca, A. Tags: Neuromuscular, Model Systems in Drug Discovery REVIEW Source Type: research
Skeletal muscle in health and disease [AT A GLANCE]
ABSTRACT
Skeletal muscle fibres are multinucleated cells that contain postmitotic nuclei (i.e. they are no longer able to divide) and perform muscle contraction. They are formed by fusion of muscle precursor cells, and grow into elongating myofibres by the addition of further precursor cells, called satellite cells, which are also responsible for regeneration following injury. Skeletal muscle regeneration occurs in most muscular dystrophies in response to necrosis of muscle fibres. However, the complex environment within dystrophic skeletal muscle, which includes inflammatory cells, fibroblasts and fibro-adipogenic cells, ...
Source: DMM Disease Models and Mechanisms - February 5, 2020 Category: Biomedical Science Authors: Morgan, J., Partridge, T. Tags: Neuromuscular AT A GLANCE Source Type: research
The latest from the preLights community - January 2020 [PREPRINT HIGHLIGHTS]
(Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - February 3, 2020 Category: Biomedical Science Tags: PREPRINT HIGHLIGHTS Source Type: research
First person - Eric Clark [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. Eric Clark is first author on ‘Establishment and validation of an endoplasmic reticulum stress reporter to monitor zebrafish ATF6 activity in development and disease’, published in DMM. Eric is a PhD student in the lab of Brian Link at the Medical College of Wisconsin, Milwaukee, WI, USA, investigating cellular stress pathways involved in neurodegeneration. (Source: DMM Disease Models and Mechanisms)
Source: DMM Disease Models and Mechanisms - January 27, 2020 Category: Biomedical Science Tags: FIRST PERSON Source Type: research
Establishment and validation of an endoplasmic reticulum stress reporter to monitor zebrafish ATF6 activity in development and disease [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 - January 27, 2020 Category: Biomedical Science Authors: Clark, E. M., Nonarath, H. J. T., Bostrom, J. R., Link, B. A. Tags: Neurodegenerative disorders, Protein-Folding Diseases: Models & Mechanisms, Zebrafish as a Disease Model RESOURCE ARTICLE Source Type: research
