A porcine model of neurofibromatosis type 1 that mimics the human disease

JCI Insight
Katherine A WhiteJill M Weimer


Loss of the NF1 tumor suppressor gene causes the autosomal dominant condition, neurofibromatosis type 1 (NF1). Children and adults with NF1 suffer from pathologies including benign and malignant tumors to cognitive deficits, seizures, growth abnormalities, and peripheral neuropathies. NF1 encodes neurofibromin, a Ras-GTPase activating protein, and NF1 mutations result in hyperactivated Ras signaling in patients. Existing NF1 mutant mice mimic individual aspects of NF1, but none comprehensively models the disease. We describe a potentially novel Yucatan miniswine model bearing a heterozygotic mutation in NF1 (exon 42 deletion) orthologous to a mutation found in NF1 patients. NF1+/ex42del miniswine phenocopy the wide range of manifestations seen in NF1 patients, including café au lait spots, neurofibromas, axillary freckling, and neurological defects in learning and memory. Molecular analyses verified reduced neurofibromin expression in swine NF1+/ex42del fibroblasts, as well as hyperactivation of Ras, as measured by increased expression of its downstream effectors, phosphorylated ERK1/2, SIAH, and the checkpoint regulators p53 and p21. Consistent with altered pain signaling in NF1, dysregulation of calcium and sodium channels wa...Continue Reading


Jul 1, 1994·Nature Genetics·T JacksR A Weinberg
Mar 1, 1993·Neuron·David H Gutmann, F S Collins
Dec 11, 1999·Science·K CichowskiT Jacks
Dec 11, 1999·Science·K S VogelLuis F Parada
Mar 10, 2001·Cell·K Cichowski, T Jacks
Oct 5, 2001·Nature Reviews. Molecular Cell Biology·C J Sherr
May 15, 2002·Developmental Medicine and Child Neurology·Victor-F MautnerRobert A Leark
Jun 26, 2002·Neoplasia : an International Journal for Oncology Research·David H Gutmann, Marco Giovannini
Aug 13, 2002·Cloning and Stem Cells·Shawn C WalkerJorge A Piedrahita
Feb 25, 2005·AJR. American Journal of Roentgenology·Ruth LimBruce R Korf
Aug 12, 2005·Journal of Neurophysiology·Yue WangCynthia M Hingtgen
Jul 5, 2006·Seminars in Pediatric Neurology·James H Tonsgard
Jul 28, 2006·Cold Spring Harbor Symposia on Quantitative Biology·Luis F ParadaY Zhu
Jul 31, 2007·Cell·Manuel ColladoManuel Serrano
Mar 4, 2008·Pediatrics·Joseph H Hersh, American Academy of Pediatrics Committee on Genetics
May 20, 2008·American Journal of Physiology. Lung Cellular and Molecular Physiology·Christopher S RogersMichael J Welsh
Nov 13, 2008·Journal of the National Cancer Institute·Atique U AhmedAmy H Tang
Jan 23, 2009·Current Opinion in Pharmacology·Silvia BenemeiPierangelo Geppetti
Jun 23, 2009·Journal of the American Academy of Dermatology·Kevin P BoydAmy Theos
Nov 26, 2009·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Amy RosenfeldStewart Goldman
Jan 2, 2010·Neurosurgical Focus·Oren N GottfriedWilliam T Couldwell
Jan 30, 2010·The American Journal of Pathology·David K MeyerholzMichael J Welsh
Apr 30, 2010·Science Translational Medicine·David A StoltzMichael J Welsh
Jul 14, 2010·American Journal of Respiratory and Critical Care Medicine·David K MeyerholzMichael J Welsh
Jul 14, 2010·Proceedings of the National Academy of Sciences of the United States of America·Carrie ShilyanskyAlcino J Silva
Oct 12, 2010·The Cerebellum·Lianne C KrabJosef N van der Geest
Apr 5, 2011·The American Journal of Pathology·Eeva-Mari JouhilahtiJuha Peltonen
Jun 1, 2010·Translational Neuroscience·Yuying WangRajesh Khanna
Nov 18, 2011·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·José Roberto Lopes Ferraz-FilhoErika Cristina Pavarino-Bertelli
Nov 24, 2011·Developmental Medicine and Child Neurology·Ornella PiscitelliVincenzo Di Ciommo
Apr 25, 2012·Animal Cognition·Monica R P ElmoreRodney W Johnson


Feb 12, 2019·Lab Animal·Ellen P Neff
Mar 28, 2019·Molecular Neurobiology·Aubin MoutalRajesh Khanna
May 23, 2020·British Journal of Cancer·Jean-Philippe BrosseauLu Q Le
Apr 10, 2019·Acta Neuropathologica·J Stephen NixFausto J Rodriguez
Jul 4, 2020·Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery·Taylor F SmithMaria T Acosta
Mar 21, 2020·Scientific Reports·Johanna UthoffJessica C Sieren
Feb 21, 2019·Nature Reviews. Neurology·Tyler B JohnsonJill M Weimer
Oct 31, 2020·Cells·Mohammed BergougHélène Bénédetti
Dec 17, 2020·CA: a Cancer Journal for Clinicians·Lynne W ElmoreWilliam C Phelps
Feb 23, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jordan L KohlmeyerDawn E Quelle
Oct 2, 2019·Journal of Dermatological Science·Tomo KamitaniIchiro Katayama
Mar 7, 2021·International Journal of Molecular Sciences·Sara H OsumDavid A Largaespada
Mar 11, 2021·Biotechnology Journal·Vincent RoyFrançois Gros-Louis
Jun 3, 2021·International Journal of Molecular Sciences·Ryota Tamura

Methods Mentioned

targeted mutation
reverse transcription PCR
protein assay

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.

Related Papers

La Revue de médecine interne
S Pinson, Pierre Wolkenstein
CMAJ : Canadian Medical Association Journal = Journal De L'Association Medicale Canadienne
Stephen Wainer
Romanian Journal of Morphology and Embryology = Revue Roumaine De Morphologie Et Embryologie
Elena ButeicăB Stănoiu
Archives of Dermatology
S L ArnsmeierA S Paller
© 2021 Meta ULC. All rights reserved