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

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 ( Dync1h1 Loa ). 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 Dync1h1 Loa 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.