Abstract
Individuals with Down syndrome (DS) present important motor deficits that derive from altered motor development of infants and young children. DYRK1A, a candidate gene for DS abnormalities has been implicated in motor function due to its expression in motor nuclei in the adult brain, and its overexpression in DS mouse models leads to hyperactivity and altered motor learning. However, its precise role in the adult motor system, or its possible involvement in postnatal locomotor development has not yet been clarified. During the postnatal period we observed time-specific expression of Dyrk1A in discrete subsets of brainstem nuclei and spinal cord motor neurons. Interestingly, we describe for the first time the presence of Dyrk1A in the presynaptic terminal of the neuromuscular junctions and its axonal transport from the facial nucleus, suggesting a function for Dyrk1A in these structures. Relevant to DS, Dyrk1A overexpression in transgenic mice (TgDyrk1A) produces motor developmental alterations possibly contributing to DS motor phenotypes and modifies the numbers of motor cholinergic neurons, suggesting that the kinase may have a role in the development of the brainstem and spinal cord motor system.
Highlights
Down syndrome (DS) is the most frequent aneuploidy leading to mental retardation [1]
TgDyrk1A mice showed no significant differences in the achievements of physical milestones, such as fur appearance, incisor eruption, eyelid opening or permeabilisation of the auditory canal
Genetic dissection studies in mouse models showed the implication of Dyrk1A, a candidate gene for DS abnormalities, in the adult DS motor phenotypes [12,16,17,20,29,30,31,32]
Summary
Down syndrome (DS) is the most frequent aneuploidy leading to mental retardation [1]. Babies and young children with DS are late to reach motor milestones such as grasping, rolling, sitting, standing and walking. Some of those DS-associated motor deficits have been reproduced in some mouse models [6,7] and could be contributed by malfunctioning of the cerebellum [6,8,9]. DYRK1A (dualspecificity tyrosine- (Y)-phosphorylation-regulated kinase 1A) is located on HSA21 [10]. It encodes for a serine threonin kinase, that belongs to an evolutionarily conserved family of proteins involved in functions generally related with growth and development [11]
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