A novel non-human primate model of Pelizaeus-Merzbacher disease

Larry S. Sherman, Weiping Su, Amanda L. Johnson, Samuel M. Peterson, Cassandra Cullin, Tiffany Lavinder, Betsy Ferguson, Anne D. Lewis

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Pelizaeus-Merzbacher disease (PMD) is a severe hypomyelinating disorder of the central nervous system (CNS) linked to mutations in the proteolipid protein-1 (PLP1) gene. Although there are multiple animal models of PMD, few of them fully mimic the human disease. Here, we report three spontaneous cases of male neonatal rhesus macaques with the clinical symptoms of hypomyelinating disease, including intention tremors, progressively worsening motor dysfunction, and nystagmus. These animals demonstrated a paucity of CNS myelination accompanied by reactive astrogliosis, and a lack of PLP1 expression throughout white matter. Genetic analysis revealed that these animals were related to one another and that their parents carried a rare, hemizygous missense variant in exon 5 of the PLP1 gene. These animals therefore represent the first reported non-human primate model of PMD, providing a novel and valuable opportunity for preclinical studies that aim to promote myelination in pediatric hypomyelinating diseases.

Original languageEnglish (US)
Article number105465
JournalNeurobiology of Disease
Volume158
DOIs
StatePublished - Oct 2021

Keywords

  • Hypomyelination
  • Non-human primate
  • Oligodendrocytes
  • Pelizaeus-Merzbacher disease
  • Proteolipid protein

ASJC Scopus subject areas

  • Neurology

Fingerprint

Dive into the research topics of 'A novel non-human primate model of Pelizaeus-Merzbacher disease'. Together they form a unique fingerprint.

Cite this