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

Vicki J Swier; Katherine A White; David K Meyerholz; Aude Chefdeville; Rajesh Khanna; Jessica C Sieren; Dawn E Quelle; Jill M Weimer

doi:10.1371/journal.pone.0228222

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

Journal article

Open access

Peer reviewed

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

Vicki J Swier, Katherine A White, David K Meyerholz, Aude Chefdeville, Rajesh Khanna, Jessica C Sieren, Dawn E Quelle and Jill M Weimer

PloS one, Vol.15(2), pp.e0228222-e0228222

02/01/2020

DOI: 10.1371/journal.pone.0228222

PMCID: PMC7029865

PMID: 32074109

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Abstract

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.

Biology and Life Sciences

Medicine and Health Sciences

Research and Analysis Methods

Details

Title: Subtitle: Validating indicators of CNS disorders in a swine model of neurological disease
Creators: Vicki J Swier - Sanford Research
Katherine A White - Sanford Research
David K Meyerholz - Roy J. and Lucille A. Carver College of Medicine
Aude Chefdeville - University of Arizona
Rajesh Khanna - University of Arizona
Jessica C Sieren - University of Iowa
Dawn E Quelle - University of Iowa
Jill M Weimer - University of South Dakota
Resource Type: Journal article
Publication Details: PloS one, Vol.15(2), pp.e0228222-e0228222
DOI: 10.1371/journal.pone.0228222
PMID: 32074109
PMCID: PMC7029865
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science
Grant note: P20GM103548 / ; NF1 Synodos / ; P20GM103620 / ;
Alternative title: Validating CNS markers in a porcine model
Language: English
Date published: 02/01/2020
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Pathology; Neuroscience and Pharmacology
Record Identifier: 9984201123902771

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