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Genetics

  • RESEARCH ARTICLE
    Genetic background modifies vulnerability to glaucoma-related phenotypes in Lmx1b mutant mice
    Nicholas G. Tolman, Revathi Balasubramanian, Danilo G. Macalinao, Alison L. Kearney, Katharine H. MacNicoll, Christa L. Montgomery, Wilhelmine N. de Vries, Ian J. Jackson, Sally H. Cross, Krishnakumar Kizhatil, K. Saidas Nair, Simon W. M. John
    Disease Models & Mechanisms 2021 14: dmm046953 doi: 10.1242/dmm.046953 Published 19 February 2021

    Summary: We observed that Lmx1b mutant mice of different strain backgrounds vary in onset and severity of glaucoma-related phenotypes and identified a modifier locus on Chr 18. These results could increase understanding of the mechanisms underlying glaucoma.

  • RESEARCH ARTICLE
    Modulating the endoplasmic reticulum stress response attenuates neurodegeneration in a Caenorhabditis elegans model of spinal muscular atrophy
    James J. Doyle, Celine Vrancx, Claudia Maios, Audrey Labarre, Shunmoogum A. Patten, J. Alex Parker
    Disease Models & Mechanisms 2020 13: dmm041350 doi: 10.1242/dmm.041350 Published 22 December 2020

    Summary: A new non-larval-lethal C. elegans model of spinal muscular atrophy shows mild phenotypes, such as muscle cell and neuronal degeneration, and is therefore useful for testing potential drug treatments.

  • AT A GLANCE
    Modeling neurodegeneration in Caenorhabditis elegans
    Kim A. Caldwell, Corey W. Willicott, Guy A. Caldwell
    Disease Models & Mechanisms 2020 13: dmm046110 doi: 10.1242/dmm.046110 Published 26 October 2020

    Summary: While unsurpassed as an experimental system for fundamental biology, Caenorhabditis elegans remains undervalued for its translational potential. Here, we highlight significant outcomes from, and resources available for, C. elegans-based research into neurodegenerative disorders.

  • RESEARCH ARTICLE
    Genetic predisposition for increased red blood cell distribution width is an early risk factor for cardiovascular and renal comorbidities
    Xi Cheng, Blair Mell, Ahmad Alimadadi, Sarah Galla, Cameron G. McCarthy, Saroj Chakraborty, Venkatesha Basrur, Bina Joe
    Disease Models & Mechanisms 2020 13: dmm044081 doi: 10.1242/dmm.044081 Published 17 May 2020

    Summary: Our study pinpoints a quantitative trait locus for red blood cell distribution width (RDW) and provides a novel genetic rat model mimicking the clinical association of increased RDW with poor cardio-renal outcome.

  • REVIEW
    Zebrafish as a tool to study schizophrenia-associated copy number variants
    Philip D. Campbell, Michael Granato
    Disease Models & Mechanisms 2020 13: dmm043877 doi: 10.1242/dmm.043877 Published 29 April 2020

    Summary: Specific copy number variants significantly increase the risk of schizophrenia, although their mechanisms are incompletely understood. We review the zebrafish as a tool to begin to decipher the complex biology of these rare variants.

  • RESEARCH ARTICLE
    Perturbation of the titin/MURF1 signaling complex is associated with hypertrophic cardiomyopathy in a fish model and in human patients
    Yuta Higashikuse, Nishant Mittal, Takuro Arimura, Sung Han Yoon, Mayumi Oda, Hirokazu Enomoto, Ruri Kaneda, Fumiyuki Hattori, Takeshi Suzuki, Atsushi Kawakami, Alexander Gasch, Tetsushi Furukawa, Siegfried Labeit, Keiichi Fukuda, Akinori Kimura, Shinji Makino
    Disease Models & Mechanisms 2019 12: dmm041103 doi: 10.1242/dmm.041103 Published 15 November 2019

    Summary: The authors identified and characterized a medaka mutation in titin that leads to a phenotype similar to hypertrophic cardiomyopathy. Similar mutations were also observed in human patients.

  • RESEARCH ARTICLE
    Developmental origins for semilunar valve stenosis identified in mice harboring congenital heart disease-associated GATA4 mutation
    Stephanie LaHaye, Uddalak Majumdar, Jun Yasuhara, Sara N. Koenig, Adrianna Matos-Nieves, Rahul Kumar, Vidu Garg
    Disease Models & Mechanisms 2019 12: dmm036764 doi: 10.1242/dmm.036764 Published 24 June 2019

    Summary: Cellular and molecular characterization of a mutant mouse, harboring a human disease-causing GATA4 variant, identifies cellular deficits in endothelial-to-mesenchymal transition and proliferation that cause abnormal valve remodeling and resultant stenosis.

  • A MODEL FOR LIFE
    Of oncogenes and open science: an interview with Harold Varmus
    Harold Varmus
    Disease Models & Mechanisms 2019 12: dmm038919 doi: 10.1242/dmm.038919 Published 1 March 2019
  • RESEARCH ARTICLE
    A novel mutation in the NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4 (Ndufa4) gene links mitochondrial dysfunction to the development of diabetes in a rodent model
    Chana Yagil, Ronen Varadi-Levi, Yoram Yagil
    Disease Models & Mechanisms 2018 11: dmm036699 doi: 10.1242/dmm.036699 Published 20 November 2018

    Summary: Here, we report, for the first time, a major inherited mutation in a diabetes-prone animal model that adversely affects mitochondrial function and leads, through oxidative stress, to the development of diet-induced diabetes.

  • CLINICAL PUZZLE
    Understanding the aetiology and resolution of chronic otitis media from animal and human studies
    Mahmood F. Bhutta, Ruth B. Thornton, Lea-Ann S. Kirkham, Joseph E. Kerschner, Michael T. Cheeseman
    Disease Models & Mechanisms 2017 10: 1289-1300; doi: 10.1242/dmm.029983

    Summary: Chronic middle ear inflammation is a common disease. Animal models, and in particular mouse models, have been used to elucidate some potential mechanisms, including dysfunction in immune signalling, mucociliary function or Eustachian tube function.

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