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

Agostina Di Pizio, Letizia Marvaldi, Marie-Christine Birling, Nataliya Okladnikov, Luc Dupuis, Mike Fainzilber, Ida Rishal

Research output: Contribution to journalArticlepeer-review


Size homeostasis is a fundamental process in biology and is particularly important for large cells such as neurons. We previously proposed a motor-dependent length-sensing mechanism wherein reductions in microtubule motor levels would be expected to accelerate neuronal growth, and validated this prediction in dynein heavy chain 1 Loa mutant (Dync1h1Loa) sensory neurons. Here, we describe a new mouse model with a conditional deletion allele of exons 24 and 25 in Dync1h1. Homozygous Islet1-Cre-mediated deletion of Dync1h1 (Isl1-Dync1h1−/−), which deletes protein from the motor and sensory neurons, is embryonic lethal, but heterozygous animals (Isl1-Dync1h1+/−) survive to adulthood with ∼50% dynein expression in targeted cells. Isl1-Dync1h1+/− sensory neurons reveal accelerated growth, as previously reported in Dync1h1Loa neurons. Moreover, Isl1-Dync1h1+/− mice show mild impairments in gait, proprioception and tactile sensation, similar to what is seen in Dync1h1Loa mice, confirming that specific aspects of the Loa phenotype are due to reduced dynein levels. Isl1-Dync1h1+/− mice also show delayed recovery from peripheral nerve injury, likely due to reduced injury signal delivery from axonal lesion sites. Thus, conditional deletion of Dync1h1 exons 24 and 25 enables targeted studies of the role of dynein in neuronal growth.
Original languageEnglish
Article numberjcs260220
Number of pages10
JournalJournal of Cell Science
Issue number5
Early online date31 Oct 2022
StatePublished - 1 Mar 2023


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