Longitudinal phenotype development in a minipig model of neurofibromatosis type 1

Johanna Uthoff, Jared Larson, Takashi S. Sato, Emily Hammond, Kimberly E. Schroeder, Frank Rohret, Christopher S. Rogers, Dawn E. Quelle, Benjamin W. Darbro, Rajesh Khanna, Jill M. Weimer, David K. Meyerholz, Jessica C. Sieren

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article number5046
JournalScientific reports
Issue number1
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • General


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