Biology
Investigating the Role of NFkB in Neuropathy
Document Type
Poster Presentation
Location
Indianapolis, IN
Start Date
13-4-2018 2:30 PM
End Date
13-4-2018 4:00 PM
Sponsor
Bruce Carter (Vanderbilt University)
Description
Charcot-Marie-Tooth (CMT) disease is an inherited neuropathy that causes muscle atrophy due to degeneration of peripheral axons. During early development, high levels of NFκB signaling are observed in the peripheral nervous system. This early signaling plays a role in inducing the differentiation of Schwann cells forming myelin. Typically developing mice exhibit a significant decrease in Schwann cell NFκB activity while Trembler J mice demonstrate persistent elevated NFκB pathway activity. Since Trembler J mice have been proven to serve as a potential model for CMT, this study used these mice to study the impacts of constitutively active NFκB. A mouse model, IKKON, was created by crossing mice with the DHH-Cre transgene and mice possessing a stop codon before the IKK gene with two serine residues mutated to two glutamine residues in the activation loop of the kinase domain (R26StopFLikk2ca). This cross yielded offspring with constitutively active NFκB signaling in Schwann cells beginning at E12.5. In order to investigate the effects of inducing constitutive NFκB activity in mice the following outcomes were observed: IKKON myelin abnormalities, axon counts, and behavioral deficits (using a tail suspension test). The results of this study suggest that there were no significant changes in the myelin or motor control of the IKKON mice compared to wild-type mice.
Investigating the Role of NFkB in Neuropathy
Indianapolis, IN
Charcot-Marie-Tooth (CMT) disease is an inherited neuropathy that causes muscle atrophy due to degeneration of peripheral axons. During early development, high levels of NFκB signaling are observed in the peripheral nervous system. This early signaling plays a role in inducing the differentiation of Schwann cells forming myelin. Typically developing mice exhibit a significant decrease in Schwann cell NFκB activity while Trembler J mice demonstrate persistent elevated NFκB pathway activity. Since Trembler J mice have been proven to serve as a potential model for CMT, this study used these mice to study the impacts of constitutively active NFκB. A mouse model, IKKON, was created by crossing mice with the DHH-Cre transgene and mice possessing a stop codon before the IKK gene with two serine residues mutated to two glutamine residues in the activation loop of the kinase domain (R26StopFLikk2ca). This cross yielded offspring with constitutively active NFκB signaling in Schwann cells beginning at E12.5. In order to investigate the effects of inducing constitutive NFκB activity in mice the following outcomes were observed: IKKON myelin abnormalities, axon counts, and behavioral deficits (using a tail suspension test). The results of this study suggest that there were no significant changes in the myelin or motor control of the IKKON mice compared to wild-type mice.