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Hop Mice Display Synchronous Hindlimb Locomotion and a Ventrally Fused Lumbar Spinal Cord Caused by a Point Mutation in Ttc26

Bernhardt, Nadine and Memic, Fatima and Velica, Anna and Tran, Michelle A. and Vieillard, Jennifer and Sayyab, Shumaila and Chersa, Taha and Andersson, Leif and Whelan, Patrick J. and Boije, Henrik and Kullander, Klas (2022). Hop Mice Display Synchronous Hindlimb Locomotion and a Ventrally Fused Lumbar Spinal Cord Caused by a Point Mutation in Ttc26. ENeuro. 9 :2 , ENEURO.0518-21.2022
[Research article]

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Abstract

Identifying the spinal circuits controlling locomotion is critical for unravelling the mechanisms controlling the production of gaits. Development of the circuits governing left-right coordination relies on axon guidance molecules such as ephrins and netrins. To date, no other class of proteins have been shown to play a role during this process. Here, we have analyzed hop mice, which walk with a characteristic hopping gait using their hindlimbs in synchrony. Fictive locomotion experiments suggest that a local defect in the ventral spinal cord contributes to the aberrant locomotor phenotype. Hop mutant spinal cords had severe morphologic defects, including the absence of the ventral midline and a poorly defined border between white and gray matter. The hop mice represent the first model where, exclusively found in the lumbar domain, the left and right components of the central pattern generators (CPGs) are fused with a synchronous hindlimb gait as a functional consequence. These defects were associated with abnormal developmental processes, including a misplaced notochord and reduced induction of ventral progenitor domains. Whereas the underlying mutation in hop mice has been suggested to lie within the Ttc26 gene, other genes in close vicinity have been associated with gait defects. Mouse embryos carrying a CRISPR replicated point mutation within Ttc26 displayed an identical morphologic phenotype. Thus, our data suggest that the assembly of the lumbar CPG network is dependent on fully functional TTC26 protein.

Authors/Creators:Bernhardt, Nadine and Memic, Fatima and Velica, Anna and Tran, Michelle A. and Vieillard, Jennifer and Sayyab, Shumaila and Chersa, Taha and Andersson, Leif and Whelan, Patrick J. and Boije, Henrik and Kullander, Klas
Title:Hop Mice Display Synchronous Hindlimb Locomotion and a Ventrally Fused Lumbar Spinal Cord Caused by a Point Mutation in Ttc26
Series Name/Journal:ENeuro
Year of publishing :2022
Volume:9
Number:2
Article number:ENEURO.0518-21.2022
Number of Pages:20
Publisher:SOC NEUROSCIENCE
Language:English
Publication Type:Research article
Article category:Scientific peer reviewed
Version:Published version
Copyright:Creative Commons: Attribution 4.0
Full Text Status:Public
Subjects:(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Neurosciences
(A) Swedish standard research categories 2011 > 1 Natural sciences > 106 Biological Sciences (Medical to be 3 and Agricultural to be 4) > Developmental Biology
Keywords:central pattern generator, midline fusion, rabbit-like gait, sonic hedgehog, spinal cord, synchrony
URN:NBN:urn:nbn:se:slu:epsilon-p-116677
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-p-116677
Additional ID:
Type of IDID
DOI10.1523/ENEURO.0518-21.2022
Web of Science (WoS)000771792500001
ID Code:27625
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Animal Breeding and Genetics
Deposited By: SLUpub Connector
Deposited On:26 Apr 2022 09:26
Metadata Last Modified:26 Apr 2022 09:31

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