CRISPR/Cas9 editing of Nf1 gene identifies CRMP2 as a therapeutic target in neurofibromatosis type 1-related pain that is reversed by (S)-Lacosamide

Aubin MoutalRajesh Khanna


Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disease linked to mutations of the Nf1 gene. Patients with NF1 commonly experience severe pain. Studies on mice with Nf1 haploinsufficiency have been instructive in identifying sensitization of ion channels as a possible cause underlying the heightened pain suffered by patients with NF1. However, behavioral assessments of Nf1 mice have led to uncertain conclusions about the potential causal role of Nf1 in pain. We used the clustered regularly interspaced short palindromic repeats (CRISPR)-associated 9 (CRISPR/Cas9) genome editing system to create and mechanistically characterize a novel rat model of NF1-related pain. Targeted intrathecal delivery of guide RNA/Cas9 nuclease plasmid in combination with a cationic polymer was used to generate allele-specific C-terminal truncation of neurofibromin, the protein encoded by the Nf1 gene. Rats with truncation of neurofibromin, showed increases in voltage-gated calcium (specifically N-type or CaV2.2) and voltage-gated sodium (particularly tetrodotoxin-sensitive) currents in dorsal root ganglion neurons. These gains-of-function resulted in increased nociceptor excitability and behavioral hyperalgesia. The cytosolic regulatory pr...Continue Reading


Jul 1, 1994·Nature Genetics·T JacksR A Weinberg
Jul 1, 1994·Journal of Neuroscience Methods·S R ChaplanT L Yaksh
Apr 26, 1996·Journal of Medicinal Chemistry·D ChoiH Kohn
Mar 27, 1999·Brain : a Journal of Neurology·A CréangePierre Wolkenstein
Nov 16, 2001·Archives of Dermatology·Pierre WolkensteinA Leplège
Dec 1, 1976·Physiology & Behavior·T L Yaksh, T A Rudy
Aug 4, 2004·Brain : a Journal of Neurology·Alain DrouetAlain Créange
Aug 12, 2005·Journal of Neurophysiology·Yue WangC M Hingtgen
Mar 4, 2008·Biochemical and Biophysical Research Communications·Yi-Ling Lin, Yi-Ping Hsueh
Dec 18, 2008·Dermatology : International Journal for Clinical and Investigative Dermatology·Yllka KodraDomenica Taruscio
Jun 1, 2010·Translational Neuroscience·Yuying WangRajesh Khanna
Oct 2, 2012·FEBS Letters·Joel M BrittainRajesh Khanna
Dec 13, 2012·Nature Reviews. Neuroscience·Sulayman D Dib-HajjStephen G Waxman
Apr 13, 2013·The Journal of Pain : Official Journal of the American Pain Society·Daniel E O'BrienRobert W Gereau
Jul 10, 2013·The Journal of Biological Chemistry·Erik T DustrudeRajesh Khanna
Jul 23, 2013·Nature Biotechnology·Patrick D HsuFeng Zhang
Oct 26, 2013·Nature Protocols·F Ann RanFeng Zhang
Jul 16, 2014·Oncotarget·Yoon-Sim YapDavid F Callen
Sep 23, 2014·Nature Neuroscience·Andrei I MoloshAnantha Shekhar
Dec 3, 2014·Molecular Therapy. Nucleic Acids·Thomas J CradickGang Bao
Apr 22, 2015·Journal of Genetic Counseling·Hilda A CrawfordKathryn N North


Apr 19, 2018·Expert Opinion on Therapeutic Targets·James A Walker, Meena Upadhyaya
Aug 25, 2017·Channels·Aubin MoutalRajesh Khanna
Feb 9, 2019·Biomaterials Science·Joon Eoh, Luo Gu
Jun 7, 2019·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Lee A CampbellBrandon K Harvey
Dec 7, 2019·Journal of Molecular Neuroscience : MN·Zhongqi ZhangGuoqing Guo
May 31, 2019·Pain·Daniel BullockMichael Costigan
Mar 28, 2019·Molecular Neurobiology·Aubin MoutalRajesh Khanna
Jan 17, 2019·Brain : a Journal of Neurology·Bianca T A de GreefIngemar S J Merkies
Dec 20, 2018·Molecular Neurobiology·Jie YuRajesh Khanna
Oct 27, 2018·Neuronal Signaling·Lindsey A Chew, Rajesh Khanna
Jun 22, 2018·JCI Insight·Katherine A WhiteJill M Weimer
Nov 5, 2019·Channels·Aubin MoutalRajesh Khanna
Aug 11, 2020·Pain·Kimberly GomezRajesh Khanna
Oct 31, 2020·Cells·Mohammed BergougHélène Bénédetti
Dec 29, 2020·Neurobiology of Disease·Chinnasamy DhanalakshmiMark A Nelson
Jul 26, 2019·Neurobiology of Disease·Udaiyappan JanakiramanMark A Nelson
Apr 16, 2018·Neuroscience·Aubin MoutalRajesh Khanna
May 8, 2021·Frontiers in Genetics·Vanessa ChenouardIgnacio Anegon

Related Concepts

Related Feeds

CRISPR Ribonucleases Deactivation

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on mechanisms that underlie deactivation of CRISPR ribonucleases. Here is the latest research.

Allergy and Asthma

Allergy and asthma are inflammatory disorders that are triggered by the activation of an allergen-specific regulatory t cell. These t cells become activated when allergens are recognized by allergen-presenting cells. Here is the latest research on allergy and asthma.

CRISPR for Genome Editing

Genome editing technologies enable the editing of genes to create or correct mutations. Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). Here is the latest research on the use of CRISPR-Cas system in gene editing.

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.