A Novel Phenotype for the Dynein Heavy Chain Mutation Loa: Altered Dendritic Morphology, Organelle Density, and Reduced Numbers of Trigeminal Motoneurons

Dynein, the retrograde motor protein, is essential for the transport of cargo along axons and proximal dendrites in neurons. The dynein heavy chain mutation Loa has been reported to cause degeneration of spinal motor neurons, as well as defects of spinal sensory proprioceptive neurons, but cranial nerve nuclei have received little attention. Here, we examined the number and morphology of neurons in cranial nerve nuclei of young, adult, and aged heterozygous Loa mice, with a focus on the trigeminal, facial, and trochlear motor nuclei, as well as the proprioceptive mesencephalic trigeminal nucleus. By using stereological counting techniques, we report a slowly progressive and significant reduction, to 75% of wild-type controls, in the number of large trigeminal motoneurons, whereas normal numbers were found for sensory mesencephalic trigeminal, facial, and trochlear motoneurons. The morphology of many surviving large trigeminal motoneurons was substantially altered, in particular the size and length of perpendicularly extending primary dendrites, but not those of facial or trochlear motoneurons. At the ultrastructural level, proximal dendrites of large trigeminal motoneurons, but not other neurons, were significantly depleted in organelle content such as polyribosomes and showed abnormal (vesiculated) mitochondria. These data indicate primary defects in trigeminal alpha-motoneurons more than gamma-motoneurons. Our findings expand the Loa heterozygote phenotype in two important ways: we reveal dendritic in addition to axonal defects or abnormalities, and we identify the Loa mutation as a mouse model for mixed motor-sensory loss when the entire neuraxis is considered, rather than a model primarily for sensory loss. J. Comp. Neurol. 520: 2757-2773, 2012. (C) 2012 Wiley Periodicals, Inc.