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Peer-reviewedCC BY 4.0Animal Models and Experimental Medicine

A rhesus macaque model of α‐dystroglycanopathy caused by a POMT1 splice altering variant

  • Anya Nordlund1
  • Brian LaMendola1
  • Nathan P. Crilly1
  • Seth Kittle1
  • Betsy M. Ferguson2
  • Anne D. Lewis1
  • Jeff Wall2
  • Samuel M. Peterson1,2
  1. 1Division of Comparative Medicine, Oregon National Primate Research Center Oregon Health & Science University Beaverton Oregon USA
  2. 2Division of Genetics, Oregon National Primate Research Center Oregon Health & Science University Beaverton Oregon USA
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Abstract

Background: Biallelic mutations in genes associated with α‐dystroglycan glycosylation manifest in a spectrum of conditions referred to as α‐dystroglycanopathies, including Walker–Warburg syndrome, which primarily disrupt brain, eye, and muscle development. While small‐animal models for the disease have been developed and described, the condition has not been documented in non‐human primates.

Methods: Three spontaneous cases of severe lissencephaly, microphthalmia, and congenital muscular contracture in infant rhesus macaques were investigated. Histological analysis was performed on brain, retina, and skeletal muscle tissue. Genomic sequencing and RT‐PCR were used to identify and validate the causative pathogenic variant.

Results: The genetic basis for disease was determined to be the result of a rare single nucleotide variant altering a canonical splice site in the POMT1 gene. Aberrant splicing was confirmed in affected monkeys and H&E staining demonstrated histological markers consistent with severe α‐dystroglycanopathy.

Conclusions: Recapitulation of this clinical disease phenotype in a non‐human primate establishes the utility of rhesus macaques as a model for dystroglycanopathies, such as Walker–Warburg syndrome.

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Cite

BibTeXRIS
BibTeX
@article{nordlund2026rhesus,
  title = {{A rhesus macaque model of α‐dystroglycanopathy caused by a POMT1 splice altering variant}},
  author = {Anya Nordlund and Brian LaMendola and Nathan P. Crilly and Seth Kittle and Betsy M. Ferguson and Anne D. Lewis and Jeff Wall and Samuel M. Peterson},
  journal = {Animal Models and Experimental Medicine},
  year = {2026},
  month = aug,
  doi = {10.1002/ame2.70277},
  url = {https://doi.org/10.1002/ame2.70277},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - A rhesus macaque model of α‐dystroglycanopathy caused by a POMT1 splice altering variant
AU  - Anya Nordlund
AU  - Brian LaMendola
AU  - Nathan P. Crilly
AU  - Seth Kittle
AU  - Betsy M. Ferguson
AU  - Anne D. Lewis
AU  - Jeff Wall
AU  - Samuel M. Peterson
PY  - 2026
DA  - 2026/08/24
JO  - Animal Models and Experimental Medicine
DO  - 10.1002/ame2.70277
UR  - https://doi.org/10.1002/ame2.70277
AB  - Background: Biallelic mutations in genes associated with α‐dystroglycan glycosylation manifest in a spectrum of conditions referred to as α‐dystroglycanopathies, including Walker–Warburg syndrome, which primarily disrupt brain, eye, and muscle development. While small‐animal models for the disease have been developed and described, the condition has not been documented in non‐human primates.  Methods: Three spontaneous cases of severe lissencephaly, microphthalmia, and congenital muscular contracture in infant rhesus macaques were investigated. Histological analysis was performed on brain, retina, and skeletal muscle tissue. Genomic sequencing and RT‐PCR were used to identify and validate the causative pathogenic variant.  Results: The genetic basis for disease was determined to be the result of a rare single nucleotide variant altering a canonical splice site in the POMT1 gene. Aberrant splicing was confirmed in affected monkeys and H&E staining demonstrated histological markers consistent with severe α‐dystroglycanopathy.  Conclusions: Recapitulation of this clinical disease phenotype in a non‐human primate establishes the utility of rhesus macaques as a model for dystroglycanopathies, such as Walker–Warburg syndrome.
SN  - 2096-5451
SN  - 2576-2095
ER  -