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A conditional null allele of Dync1h1 enables targeted analyses of dynein roles in neuronal length sensing and neurological disorders

View ORCID ProfileAgostina Di Pizio, View ORCID ProfileLetizia Marvaldi, View ORCID ProfileMarie-Christine Birling, View ORCID ProfileNataliya Okladnikov, View ORCID ProfileLuc Dupuis, View ORCID ProfileMike Fainzilber, View ORCID ProfileIda Rishal
doi: https://doi.org/10.1101/2022.02.20.481176
Agostina Di Pizio
1Departments of Biomolecular Sciences and Molecular Neuroscience, Weizmann Institute of Science, Rehovot 76100, Israel
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Letizia Marvaldi
1Departments of Biomolecular Sciences and Molecular Neuroscience, Weizmann Institute of Science, Rehovot 76100, Israel
2Department of Neuroscience “Rita Levi Montalcini,” Neuroscience Institute Cavalieri Ottolenghi, University of Turin, Orbassano, Italy
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Marie-Christine Birling
3PHENOMIN-Institut Clinique de la Souris, Université de Strasbourg, Illkirch, France
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Nataliya Okladnikov
1Departments of Biomolecular Sciences and Molecular Neuroscience, Weizmann Institute of Science, Rehovot 76100, Israel
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Luc Dupuis
4INSERM U1118, Université de Strasbourg, 67085 Strasbourg, France
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Mike Fainzilber
1Departments of Biomolecular Sciences and Molecular Neuroscience, Weizmann Institute of Science, Rehovot 76100, Israel
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Ida Rishal
1Departments of Biomolecular Sciences and Molecular Neuroscience, Weizmann Institute of Science, Rehovot 76100, Israel
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  • For correspondence: ida.rishal@weizmann.ac.il
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Abstract

Size homeostasis is one of the most fundamental aspects of biology and it is particularly important for large cells as neurons. We have previously proposed a motor-dependent length-sensing and growth-regulating mechanism wherein a partial reduction in the levels of microtubule motor proteins should lead to accelerated neuronal growth. This prediction was originally validated in sensory neurons heterozygous for the Loa point mutation in dynein heavy chain 1 (Dync1h1Loa). Here we describe a new mouse model with a conditional allele allowing deletion of exons 24-25 in Dync1h1. Homozygous Islet1-Cre deletion of Dync1h1 is embryonic lethal, but heterozygous animals (Isl1-Dync1h1+/−) survive to adulthood with approximately 50% dynein expression in targeted cell types. Isl1-Dync1h1+/− adult sensory neurons reveal an accelerated growth phenotype, similar to that previously reported in Dync1h1Loa neurons. Moreover, Isl1-Dync1h1+/− mice show mild impairments in gait, proprioception and tactile sensation; and slightly impaired recovery from peripheral nerve injury. Thus, conditional deletion of Dync1h1 exons 24-25 enables targeted studies of the role of dynein in neuronal growth and neurological disorders.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted February 20, 2022.
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A conditional null allele of Dync1h1 enables targeted analyses of dynein roles in neuronal length sensing and neurological disorders
Agostina Di Pizio, Letizia Marvaldi, Marie-Christine Birling, Nataliya Okladnikov, Luc Dupuis, Mike Fainzilber, Ida Rishal
bioRxiv 2022.02.20.481176; doi: https://doi.org/10.1101/2022.02.20.481176
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A conditional null allele of Dync1h1 enables targeted analyses of dynein roles in neuronal length sensing and neurological disorders
Agostina Di Pizio, Letizia Marvaldi, Marie-Christine Birling, Nataliya Okladnikov, Luc Dupuis, Mike Fainzilber, Ida Rishal
bioRxiv 2022.02.20.481176; doi: https://doi.org/10.1101/2022.02.20.481176

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