Review
Biochemistry & Molecular Biology
Elizaveta A. A. Olkhova, Laura A. A. Smith, Carla Bradshaw, Grainne S. Gorman, Daniel Erskine, Yi Shiau Ng
Summary: Mitochondrial diseases are common genetic neurometabolic disorders that currently lack effective therapies. This review discusses various mouse models with transgenic impairments in genes regulating mitochondrial function, focusing on their neurological phenotype and neuropathological features. Most mouse models exhibit ataxia, similar to patients, and share the neuropathological finding of Purkinje neuron loss. However, none of the existing models fully recapitulate the severe neurological phenotypes seen in patients, such as refractory focal seizures and stroke-like episodes. The roles of reactive astrogliosis and microglial reactivity in driving neuropathology, as well as alternative mechanisms of cellular death in neurons during mitochondrial bioenergy crisis, are also discussed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Meredith A. Mortberg, Eric Vallabh Minikel, Sonia M. Vallabh
Summary: Research suggests that testing the efficacy of prion disease therapies in non-human primates (NHPs) poses challenges, requiring pilot studies to confirm incubation time and attack rate, which can take several years.
Review
Medicine, General & Internal
Justin Choi, Nishadh Sutaria, Youkyung Sophie Roh, Zachary Bordeaux, Martin P. Alphonse, Shawn G. Kwatra, Madan M. Kwatra
Summary: The complexity of atopic dermatitis poses a challenge in selecting an appropriate mouse model, as no single model can fully replicate all aspects of the human condition. Recent evidence has identified distinct endotypes of AD, characterized by unique patterns of inflammation involving Th1, Th2, Th17, and Th22 axes. While all AD mouse models consistently show Th2 inflammation, only some also exhibit Th17 and/or Th22 induction, highlighting the need for a closer evaluation of their immunological signature to enhance their relevance to human AD.
JOURNAL OF CLINICAL MEDICINE
(2021)
Editorial Material
Biochemistry & Molecular Biology
Kathryn M. Edwards, Kathleen M. Neuzil
Summary: As the pandemic progresses, conducting field studies becomes increasingly challenging, but human challenge models could serve as a practical and timely solution.
Review
Biochemistry & Molecular Biology
Chuangen Li, Harry Cheuk-Hay Lau, Xiang Zhang, Jun Yu
Summary: This review explores the overall features and mechanisms of carcinogen-induced and transgenic mouse models for colon tumorigenesis, as well as their limitations and applications in evaluating and studying drugs and treatment regimens against CRC. These mouse models provide a better understanding of the mechanisms of colon tumorigenesis and facilitate the discovery of novel therapeutic strategies against CRC.
Article
Pharmacology & Pharmacy
Qin Hui Li, Kenneth Kim, Sujan Shresta
Summary: Seven years after the onset of the Zika virus epidemic, longitudinal studies have shown that children infected in utero without severe birth defects exhibit motor skill deficits at up to 3 years of age. The long-term health and socioeconomic impacts of fetal Zika virus infection seem inevitable. In the absence of vaccines or antivirals, small animal models of Zika virus transmission are essential to test antiviral strategies and understand the mechanisms of immunity at the maternal-fetal interface. The review discusses the current state of Zika virus transplacental transmission models, highlights key unanswered questions, and sets goals for the next generation of mouse models.
ANTIVIRAL RESEARCH
(2023)
Review
Anatomy & Morphology
Michael T. Yarboro, Srirupa H. Gopal, Rachel L. Su, Thomas M. Morgan, Jeff Reese
Summary: The ductus arteriosus is a unique fetal vascular shunt that allows blood to bypass the developing lungs in utero. After birth, changes in signaling pathways lead to constriction and closure of the ductus arteriosus. Persistent ductus arteriosus is common in preterm infants, but the underlying causes are not fully defined. Mouse models have been used to study critical pathways in ductus arteriosus regulation.
DEVELOPMENTAL DYNAMICS
(2022)
Article
Multidisciplinary Sciences
Wiebke Winkler, Carlota Farre Diaz, Eric Blanc, Hanna Napieczynska, Patrick Langner, Marvin Werner, Barbara Walter, Brigitte Wollert-Wulf, Tomoharu Yasuda, Arnd Heuser, Dieter Beule, Stephan Mathas, Ioannis Anagnostopoulos, Andreas Rosenwald, Klaus Rajewsky, Martin Janz
Summary: By targeting the expression of genes involved in MM subgroup-specific chromosomal translocations into mouse GC B cells, we have generated distinct MM-like disease models that recapitulate key features of human tumors, which provides insights into the pathogenesis and therapeutic vulnerabilities of different MM subgroups.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Physiology
Christopher A. Waker, Melissa R. Kaufman, Thomas L. Brown
Summary: Preeclampsia is a pregnancy-specific disorder associated with abnormal placentation, and the only definitive treatment is delivery. Various mouse models have been developed to simulate PE and investigate the molecular mechanisms involved in the human condition, but standardizing physiological characteristics for analysis is important for accurate comparisons and therapeutic development.
FRONTIERS IN PHYSIOLOGY
(2021)
Review
Microbiology
Ivana Kutle, Anne Dittrich, Dagmar Wirth
Summary: More than hundred herpesviruses have been identified, but only nine infect humans. Infections with herpesviruses pose a significant challenge to human health due to lifelong latency. Mouse models, particularly immunocompromised mice and xenograft mice, have been developed to study herpesvirus infections and human-restricted viruses. This review focuses on the various mouse models used in herpesvirus research, with an emphasis on xenograft models.
Review
Neurosciences
Eunice Eun Seo Chang, Philip Wing-Lok Ho, Hui-Fang Liu, Shirley Yin-Yu Pang, Chi-Ting Leung, Yasine Malki, Zoe Yuen-Kiu Choi, David Boyer Ramsden, Shu-Leong Ho
Summary: Mutations in the LRRK2 gene are common causes of Parkinson's disease and suggest that LRRK2 could be a therapeutic target. LRRK2 mutant mice models show pathological similarities to early-stage Parkinson's disease, providing important insights into the mechanisms of the disease.
TRANSLATIONAL NEURODEGENERATION
(2022)
Review
Immunology
Yinxi Zhou, Jinghua Xia, Shuonan Xu, Tao She, Yanning Zhang, Ying Sun, Miaomiao Wen, Tao Jiang, Yanlu Xiong, Jie Lei
Summary: The development and growth of tumors pose a significant and ongoing threat to human life globally. Despite the remarkable progress achieved by advanced therapeutic strategies such as immune checkpoint therapy and CAR-T in treating solid and hematological malignancies, the malignant initiation and progression of cancer remains controversial and requires further research. Experimental animal models not only have great advantages in simulating tumor occurrence, development, and malignant transformation mechanisms, but also can be used to evaluate the therapeutic effects of diverse clinical interventions, gradually becoming indispensable in cancer research. This paper reviews recent research progress in mouse and rat models, focusing on spontaneous, induced, transgenic, and transplantable tumor models, aiming to provide guidance for future studies on malignant mechanisms and tumor prevention.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Public, Environmental & Occupational Health
Amar Aganovic, Edin Kadric
Summary: The risk assessments during the COVID-19 pandemic were primarily based on dose-response models, but differences in susceptibility exist between animal and human respiratory viruses. The exponential model and Stirling approximated beta-Poisson (BP) model are commonly used, but the Stirling approximation has limitations. A novel BP model using the Laplace approximation was tested, and the exponential model was found to be the best fit for HCoV-229E and HRV-39 datasets. The Laplace approximated BP model was preferred for HRV-16 and pooled datasets.
Review
Endocrinology & Metabolism
Manita Shakya, Iris Lindberg
Summary: This review discusses the structure, function, and association with human diseases of kexin-like proprotein convertases, highlighting the limitations and challenges of using mouse models in elucidating disease mechanisms and human diseases.
Article
Cell Biology
Dongli Liang, Qi Sun, Zijue Zhu, Chuanyun Wang, Shicheng Ye, Zheng Li, Yuan Wang
Summary: This study found that genetically infertile mice can be suitable recipients for xenotransplantation of human germ cells, with minimal immunological rejection from immune-competent mouse recipients. The researchers also derived spermatogonia-like cells (SLCs) from human pluripotent stem cells (PSCs), which showed colonization and proliferation in transplanted mouse recipients. This study functionally defined the cell identity of PSC-derived SLCs and supported the use of genetically infertile recipients as a convenient model for evaluating spermatogonia from different species.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Clinical Neurology
Philipp Sievers, Martin Sill, Christina Blume, Arnault Tauziede-Espariat, Daniel Schrimpf, Damian Stichel, David E. Reuss, Helin Dogan, Christian Hartmann, Christian Mawrin, Martin Hasselblatt, Walter Stummer, Uta Schick, Jurgen Hench, Stephan Frank, Ralf Ketter, Leonille Schweizer, Jens Schittenhelm, Stephanie Puget, Sebastian Brandner, Zane Jaunmuktane, Benno Kusters, Zied Abdullaev, Melike Pekmezci, Matija Snuderl, Miriam Ratliff, Christel Herold-Mende, Andreas Unterberg, Kenneth Aldape, David W. Ellison, Pieter Wesseling, Guido Reifenberger, Wolfgang Wick, Arie Perry, Pascale Varlet, Stefan M. Pfister, David T. W. Jones, Andreas von Deimling, Felix Sahm
Summary: The study explores the molecular characteristics of clear cell meningioma, revealing a distinct epigenetic signature and recurrent mutations in the SMARCE1 gene. Patients with clear cell meningioma show a similar prognosis to those with meningioma WHO grade 2, supporting the classification of these tumors as WHO grade 2.
ACTA NEUROPATHOLOGICA
(2021)
Article
Clinical Neurology
S. C. Thust, J. A. Maynard, M. Benenati, S. J. Wastling, L. Mancini, Z. Jaunmuktane, S. Brandner, H. R. Jaeger
Summary: The study demonstrates that ROI and VOI ADC measurements are the most accurate for predicting IDH status in gliomas, with potential clinical applications. In specific types of tumors, volumetric measurements are more predictive than ROI, suggesting different types of tumors may require different ADC measurement methods.
AMERICAN JOURNAL OF NEURORADIOLOGY
(2021)
Review
Clinical Neurology
Ana Belen Diaz Mendez, Elisa Tremante, Giulia Regazzo, Sebastian Brandner, Maria G. Rizzo
Summary: Gliomas are tumors that originate from progenitors within the central nervous system, with a majority requiring surgical intervention and having a tendency to recur. Imaging has limitations in monitoring tumor burden post-surgery, and liquid biopsies show promise in aiding diagnosis and prognosis.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
Correction
Radiology, Nuclear Medicine & Medical Imaging
John Maynard, Sachi Okuchi, Stephen Wastling, Ayisha Al Busaidi, Ofran Almossawi, Wonderboy Mbatha, Sebastian Brandner, Zane Jaunmuktane, Ali Murat Koc, Laura Mancini, Rolf Jager, Stefanie Thust
Article
Immunology
Jonathan D. F. Wadsworth, Susan Joiner, Jacqueline M. Linehan, Kezia Jack, Huda Al-Doujaily, Helena Costa, Thea Ingold, Maged Taema, Fuquan Zhang, Malin K. Sandberg, Sebastian Brandner, Linh Tran, Turid Vikoren, Jorn Vage, Knut Madslien, Bjornar Ytrehus, Sylvie L. Benestad, Emmanuel A. Asante, John Collinge
Summary: This study investigated the zoonotic potential of CWD-infected Norwegian reindeer and moose by inoculating their brain tissue into transgenic mice overexpressing human prion protein. The results showed no evidence of prion transmission, indicating a low zoonotic potential for these isolates.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Multidisciplinary Sciences
Lucy J. Brooks, Melanie P. Clements, Jemima J. Burden, Daniela Kocher, Luca Richards, Sara Castro Devesa, Leila Zakka, Megan Woodberry, Michael Ellis, Zane Jaunmuktane, Sebastian Brandner, Gillian Morrison, Steven M. Pollard, Peter B. Dirks, Samuel Marguerat, Simona Parrinello
Summary: The study reveals that glioblastoma cells infiltrating into the white matter acquire a pre-oligodendrocyte-like fate, leading to decreased proliferation and invasion of tumors. This differentiation is a response to white matter injury, driven by the upregulation of SOX10. Additionally, the study suggests that exploiting this latent program may offer treatment opportunities for a subset of patients.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Tuyu Zheng, David R. Ghasemi, Konstantin Okonechnikov, Andrey Korshunov, Martin Sill, Kendra K. Maass, Patricia Benites Goncalves da Silva, Marina Ryzhova, Johannes Gojo, Damian Stichel, Amir Arabzade, Robert Kupp, Julia Benzel, Shinichiro Taya, Toma Adachi, Ryo Shiraishi, Nicolas U. Gerber, Dominik Sturm, Jonas Ecker, Philipp Sievers, Florian Selt, Rebecca Chapman, Christine Haberler, Dominique Figarella-Branger, Guido Reifenberger, Gudrun Fleischhack, Stefan Rutkowski, Andrew M. Donson, Vijay Ramaswamy, David Capper, David W. Ellison, Christel C. Herold-Mende, Ulrich Schueller, Sebastian Brandner, Pablo Hernaiz Driever, Johan M. Kros, Matija Snuderl, Till Milde, Richard G. Grundy, Mikio Hoshino, Stephen C. Mack, Richard J. Gilbertson, David T. W. Jones, Marcel Kool, Andreas von Deimling, Stefan M. Pfister, Felix Sahm, Daisuke Kawauchi, Kristian W. Pajtler
Summary: Supratentorial ependymomas can be categorized into tumors with ZFTA-RELA or YAP1 fusions, fusion-negative subependymomas, and other tumors that cannot be classified. ZFTA acts as a partner gene in oncogenic fusions with various histologic features, with GLI2 identified as a key regulator of tumorigenesis in these tumors. Targeting GLI2 with arsenic trioxide shows potential therapeutic benefits for ZFTA fusion-positive tumors.
Article
Clinical Neurology
Zane Jaunmuktane, Gargi Banerjee, Simon Paine, Adrian Parry-Jones, Peter Rudge, Joan Grieve, Ahmed K. Toma, Simon F. Farmer, Simon Mead, Henry Houlden, David J. Werring, Sebastian Brandner
ACTA NEUROPATHOLOGICA
(2021)
Article
Pathology
Wolfram Breuer, Sebastian Brandner, Angela Hafner-Marx
Summary: Tumours of the nervous system are rare in wild and captive mammals. The report describes an intracranial solid lesion originating from the meninges in a Nilgai antelope, which histologically resembles the microcystic meningioma subtype in humans, making it the first such tumour reported in this species.
JOURNAL OF COMPARATIVE PATHOLOGY
(2021)
Article
Multidisciplinary Sciences
Szymon W. Manka, Wenjuan Zhang, Adam Wenborn, Jemma Betts, Susan Joiner, Helen R. Saibil, John Collinge, Jonathan D. F. Wadsworth
Summary: The high-resolution structure of mammalian prions has been determined using cryo-EM, revealing a common architecture among different animal species. These findings provide important insights into the propagation of prions and the differences between different prion strains.
NATURE COMMUNICATIONS
(2022)
Review
Cell Biology
Szymon W. Manka, Adam Wenborn, John Collinge, Jonathan D. F. Wadsworth
Summary: Mammalian prions are deadly transmissible pathogens that cause neurodegenerative diseases in humans and animals. There are still important gaps in our understanding of prion biology, including the replication mechanisms, molecular basis of prion strains and inter-species transmission barriers, and the structural definition of neurotoxic PrP species. Recent advances in cryo-electron microscopy have made it possible to determine the structures of ex vivo prion fibrils, providing a foundation for understanding prion strain diversity.
CELL AND TISSUE RESEARCH
(2023)
Article
Multidisciplinary Sciences
Graham S. Jackson, Jacqueline Linehan, Sebastian Brandner, Emmanuel A. Asante, Jonathan D. F. Wadsworth, John Collinge
Summary: Transgenic mice have provided valuable insights into the understanding of human prion diseases and the study of protein misfolding in neurodegenerative diseases. Overexpression of the wild-type mouse prion protein can cause a protein misfolding disorder similar to authentic prion disease.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Szymon W. Manka, Adam Wenborn, Jemma Betts, Susan Joiner, Helen R. Saibil, John Collinge, Jonathan D. F. Wadsworth
Summary: Recent cryo-EM studies revealed a similar amyloid architecture in infectious prion fibrils from different strains. This study determined the cryo-EM structure of mouse prion fibrils from two prion strains, ME7 and RML, and compared their folding subdomains. The results provide a structural definition of strain-specific conformations in prion diseases.
NATURE CHEMICAL BIOLOGY
(2023)
Review
Medicine, General & Internal
Alexandra McAleenan, Claire Kelly, Francesca Spiga, Ashleigh Kernohan, Hung-Yuan Cheng, Sarah Dawson, Lena Schmidt, Tomos Robinson, Sebastian Brandner, Claire L. Faulkner, Christopher Wragg, Sarah Jefferies, Amy Howell, Luke Vale, Julian P. T. Higgins, Kathreena M. Kurian
Summary: This study focuses on determining the most accurate method for assessing MGMT methylation status in patients with glioblastoma treated with temozolomide. Results show that MSP and PSQ methods are more prognostic for overall survival than IHC. It suggests that PSQ may be slightly more prognostic than MSP, and targeted multiple CpG sites may be more effective than targeting just one.
COCHRANE DATABASE OF SYSTEMATIC REVIEWS
(2021)