Using a mouse model to gain insights into developmental coordination disorder

Abstract

Motor impairments are a common feature of many neurodevelopmental disorders; in fact, over 50% of children with Attentional Deficit Hyperactivity Disorder or Autism Spectrum Disorder may have a co‐occurring diagnosis of developmental coordination disorder (DCD). DCD is a neurodevelopmental disorder of unknown etiology that affects motor coordination and learning, significantly impacting a child's ability to carry out everyday activities. Animal models play an important role in scientific investigation of behaviour and the mechanisms and processes that are involved in control of motor actions. The purpose of this paper is to present an approach in the mouse directed to gain behavioral and genetic insights into DCD that is designed with high face validity, construct validity and predictive validity. Pre‐clinical and clinical expertise is used to establish a set of scientific criteria that the model will meet in order to investigate the potential underlying causes of DCD.

Developmental Coordination Disorder: What Can We Learn From Recombinant Inbred Mice Using Motor Learning Tasks and Quantitative Trait Locus Analysis

“…The cerebellum’s key role in co-ordinated behaviours, postural control, and motor learning point to this structure underlying DCD. In support this hypothesis, Gill et al (2020) and Zwicker et al (2011) found structural and functional abnormalities in the cerebellum of children with DCD. Additionally, there is an indication that DCD has an underlying genetic component due to its high heritability.…”

“…Procedures: Behavioural Testing Detailed information on the study timeline is available in Figure 1 and rationale and procedural details for the behavioural tasks are outlined in Gill et al (2020). This paper focuses on the first third and last phases of the study, as outlined in Figure 1.…”

“…Longitudinal research on disorders such as attention deficit hyperactivity disorder and autism spectrum disorder have demonstrated changes in clinical symptoms and underlying neurobiology across the lifespan, highlighting the importance of examining development longitudinally; but few studies have taken a developmental perspective when examining the genotype and phenotype of motor performance as it relates to neurodevelopmental disorders. Therefore, we conceptualized a battery of motor behaviour tasks across the mouse lifespan, as presented in a recent review by Gill et al (2020). In our two-part study, we first presented the phenotypic and genotypic data for motor coordination in Gill et el.…”

Investigating mouse motor coordination using quantitative trait locus analysis to model the genetic underpinnings of developmental coordination disorder

“…8, 10 BXD 1, BXD15, BXD27, BXD28, and BXD40 were selected due to their variation in cerebellar volume. 9…”

“…To capture the motor variability seen in BXD RI mice, we devised a battery of motor behavior tasks (Figure 1) to mimic the motor deficits observed in human DCD (see Gill et al 9 for details). Using this approach, we can begin to identify candidate regions of chromosomes that harbor genes that underlie the behaviors of interest in DCD using Quantitative Trait Loci (QTL) analysis.…”