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Loss of mouse Stmn2 function causes motor neuropathy.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is characterized by motor neuron degeneration accompanied by aberrant accumulation and loss of function of the RNA-binding protein TDP43. Thus far, it remains unresolved to what extent TDP43 loss of function directly contributes to motor system dysfunction. Here, we employed gene editing to find whether the mouse ortholog of the TDP43-regulated gene STMN2 has an important function in maintaining the motor system. Both mosaic founders and homozygous loss-of-function Stmn2 mice exhibited neuromuscular junction denervation and fragmentation, resulting in muscle atrophy and impaired motor behavior, accompanied by an imbalance in neuronal microtubule dynamics in the spinal cord. The introduction of human STMN2 through BAC transgenesis was sufficient to rescue the motor phenotypes observed in Stmn2 mutant mice. Collectively, our results demonstrate that disrupting the ortholog of a single TDP43-regulated RNA is sufficient to cause substantial motor dysfunction, indicating that disruption of TDP43 function is likely a contributor to ALS.

SUBMITTER: Guerra San Juan I

PROVIDER: S-EPMC9119928 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Loss of mouse Stmn2 function causes motor neuropathy.

Guerra San Juan Irune I Nash Leslie A LA Smith Kevin S KS Leyton-Jaimes Marcel F MF Qian Menglu M Klim Joseph R JR Limone Francesco F Dorr Alexander B AB Couto Alexander A Pintacuda Greta G Joseph Brian J BJ Whisenant D Eric DE Noble Caroline C Melnik Veronika V Potter Deirdre D Holmes Amie A Burberry Aaron A Verhage Matthijs M Eggan Kevin K

Neuron 20220315 10

Amyotrophic lateral sclerosis (ALS) is characterized by motor neuron degeneration accompanied by aberrant accumulation and loss of function of the RNA-binding protein TDP43. Thus far, it remains unresolved to what extent TDP43 loss of function directly contributes to motor system dysfunction. Here, we employed gene editing to find whether the mouse ortholog of the TDP43-regulated gene STMN2 has an important function in maintaining the motor system. Both mosaic founders and homozygous loss-of-fun ...[more]

PMID: 35294901

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Loss of mouse Stmn2 function causes motor neuropathy.

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Loss of mouse Stmn2 function causes motor neuropathy.

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