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

doi:10.1038/s41598-020-61251-4

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Longitudinal phenotype development in a minipig model of neurofibromatosis type 1

Journal article

Open access

Peer reviewed

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, …

Scientific reports, Vol.10(1), pp.5046-5046

03/19/2020

DOI: 10.1038/s41598-020-61251-4

PMCID: PMC7081358

PMID: 32193437

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Abstract

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 ) 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 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 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 minipig model progressively demonstrates signature attributes that parallel clinical manifestations seen in humans and provides a viable tool for future translational NF1 research.

Magnetic Resonance Imaging

Phenotype

Animals

Disease Models, Animal

Disease Progression

Humans

Neurofibroma - diagnostic imaging

Neurofibroma - pathology

Neurofibromatosis 1 - diagnostic imaging

Neurofibromatosis 1 - pathology

Swine

Swine, Miniature

Tibia - diagnostic imaging

Tibia - pathology

Time Factors

Tomography, X-Ray Computed

Translational Medical Research

Details

Title: Subtitle: Longitudinal phenotype development in a minipig model of neurofibromatosis type 1
Creators: Johanna Uthoff - University of Iowa
Jared Larson - Department of Radiology, University of Iowa, Iowa City, IA, USA
Takashi S Sato - University of Iowa
Emily Hammond - University of Iowa
Kimberly E Schroeder - University of Iowa
Frank Rohret - Exemplar Genetics (United States)
Christopher S Rogers - Exemplar Genetics (United States)
Dawn E Quelle - University of Iowa
Benjamin W Darbro - University of Iowa
Rajesh Khanna - University of Arizona
Jill M Weimer - Sanford Research
David K Meyerholz - University of Iowa
Jessica C Sieren - University of Iowa
Resource Type: Journal article
Publication Details: Scientific reports, Vol.10(1), pp.5046-5046
DOI: 10.1038/s41598-020-61251-4
PMID: 32193437
PMCID: PMC7081358
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Grant note: P30 ES005605 / NIEHS NIH HHS S10 OD018526 / NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 03/19/2020
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Radiology; Stead Family Department of Pediatrics; Pathology; Medical Genetics and Genomics; Neuroscience and Pharmacology
Record Identifier: 9984186406702771

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