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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere0228222
JournalPloS one
Volume15
Issue number2
DOIs
StatePublished - Jan 1 2020

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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  • Cite this

    Swier, V. J., White, K. A., Meyerholz, D. K., Chefdeville, A., Khanna, R., Sieren, J. C., Quelle, D. E., & Weimer, J. M. (2020). Validating indicators of CNS disorders in a swine model of neurological disease. PloS one, 15(2), [e0228222]. https://doi.org/10.1371/journal.pone.0228222