Validating indicators of CNS disorders in a swine model of neurological disease.

Autor: Swier VJ; Pediatrics and Rare Diseases Group, Sanford Research, Sioux Falls, South Dakota, United States of America., White KA; Pediatrics and Rare Diseases Group, Sanford Research, Sioux Falls, South Dakota, United States of America., Meyerholz DK; Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America., Chefdeville A; Department of Pharmacology, College of Medicine, University of Arizona, Tucson, Arizona, United States of America., Khanna R; Department of Pharmacology, College of Medicine, University of Arizona, Tucson, Arizona, United States of America.; Graduate Interdisciplinary Program in Neuroscience; College of Medicine, University of Arizona, Tucson, Arizona, United States of America., Sieren JC; Department of Radiology and Biomedical Engineering, University of Iowa, Iowa City, Iowa, United States of America., Quelle DE; Department of Pathology, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States of America.; Department of Neuroscience and Pharmacology, University of Iowa, Iowa City, Iowa, United States of America., Weimer JM; Pediatrics and Rare Diseases Group, Sanford Research, Sioux Falls, South Dakota, United States of America.; Department of Pediatrics, Sanford School of Medicine, University of South Dakota, Sioux Falls, South Dakota, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2020 Feb 19; Vol. 15 (2), pp. e0228222. Date of Electronic Publication: 2020 Feb 19 (Print Publication: 2020).
DOI: 10.1371/journal.pone.0228222
Abstrakt: Genetically modified swine disease models are becoming increasingly important for studying molecular, physiological and pathological characteristics of human disorders. Given the limited history of these model systems, there remains a great need for proven molecular reagents in swine tissue. Here, to provide a resource for neurological models of disease, we validated antibodies by immunohistochemistry for use in examining central nervous system (CNS) markers in a recently developed miniswine model of neurofibromatosis type 1 (NF1). NF1 is an autosomal dominant tumor predisposition disorder stemming from mutations in NF1, a gene that encodes the Ras-GTPase activating protein neurofibromin. Patients classically present with benign neurofibromas throughout their bodies and can also present with neurological associated symptoms such as chronic pain, cognitive impairment, and behavioral abnormalities. As validated antibodies for immunohistochemistry applications are particularly difficult to find for swine models of neurological disease, we present immunostaining validation of antibodies implicated in glial inflammation (CD68), oligodendrocyte development (NG2, O4 and Olig2), and neuron differentiation and neurotransmission (doublecortin, GAD67, and tyrosine hydroxylase) by examining cellular localization and brain region specificity. Additionally, we confirm the utility of anti-GFAP, anti-Iba1, and anti-MBP antibodies, previously validated in swine, by testing their immunoreactivity across multiple brain regions in mutant NF1 samples. These immunostaining protocols for CNS markers provide a useful resource to the scientific community, furthering the utility of genetically modified miniswine for translational and clinical applications.
Competing Interests: Our association with Sanford Research does not alter our adherence to PLOS ONE policies on sharing data and materials. The authors have declared that no competing interests exist. The specific roles of these authors are articulated in the ‘author contributions’ section.
Databáze: MEDLINE
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