Longitudinal phenotype development in a minipig model of neurofibromatosis type 1

Sci Rep. 2020 Mar 19;10(1):5046. doi: 10.1038/s41598-020-61251-4.


Neurofibromatosis type 1 (NF1) is a rare, autosomal dominant disease with variable clinical presentations. Large animal models are useful to help dissect molecular mechanisms, determine relevant biomarkers, and develop effective therapeutics. Here, we studied a NF1 minipig model (NF1+/ex42del) for the first 12 months of life to evaluate phenotype development, track disease progression, and provide a comparison to human subjects. Through systematic evaluation, we have shown that compared to littermate controls, the NF1 model develops phenotypic characteristics of human NF1: [1] café-au-lait macules, [2] axillary/inguinal freckling, [3] shortened stature, [4] tibial bone curvature, and [5] neurofibroma. At 4 months, full body computed tomography imaging detected significantly smaller long bones in NF1+/ex42del minipigs compared to controls, indicative of shorter stature. We found quantitative evidence of tibial bowing in a subpopulation of NF1 minipigs. By 8 months, an NF1+/ex42del boar developed a large diffuse shoulder neurofibroma, visualized on magnetic resonance imaging, which subsequently grew in size and depth as the animal aged up to 20 months. The NF1+/ex42del minipig model progressively demonstrates signature attributes that parallel clinical manifestations seen in humans and provides a viable tool for future translational NF1 research.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Disease Progression
  • Humans
  • Magnetic Resonance Imaging
  • Neurofibroma / diagnostic imaging
  • Neurofibroma / pathology
  • Neurofibromatosis 1 / diagnostic imaging*
  • Neurofibromatosis 1 / pathology*
  • Phenotype*
  • Swine
  • Swine, Miniature
  • Tibia / diagnostic imaging
  • Tibia / pathology
  • Time Factors
  • Tomography, X-Ray Computed
  • Translational Research, Biomedical