Developmental coordination disorder: What can we learn from RI mice using motor learning tasks and QTL analysis

Area of Science:

• Neurogenetics
• Developmental Neuroscience
• Behavioral Genetics

Background:

• Developmental Coordination Disorder (DCD) affects approximately 5% of children and is suspected to have a genetic basis due to high heritability.
• Understanding the genetic underpinnings of DCD is crucial for developing targeted interventions and improving diagnosis.

Purpose of the Study:

• To investigate the genetic basis of DCD by analyzing motor learning deficits in a mouse model.
• To identify quantitative trait loci (QTLs) associated with DCD-like phenotypes using the BXD recombinant inbred panel.
• To evaluate the genome-to-phenome correlation for DCD in mice.

Main Methods:

• Utilized the BXD panel of recombinant inbred mice to study motor learning and identify QTLs.
• Assessed motor learning performance in various BXD strains, including those with altered cerebellar volume.
• Analyzed gene functions within significant QTLs to identify candidate genes for DCD-like behaviors.

Main Results:

• Confirmed significant differences in motor learning across selected BXD mouse strains.
• Identified five strains (BXD15, BXD27, BXD28, BXD75, BXD86) exhibiting pronounced DCD-like phenotypes.
• Observed strain-specific deficits in gross motor skills (BXD15, BXD75), fine motor skills (BXD28), or both (BXD27, BXD86).
• Rab3a (Ras-related protein Rab-3A) was identified as a high-likelihood candidate gene for horizontal ladder task performance.

Conclusions:

• The BXD mouse model is valuable for dissecting the genetic architecture of DCD.
• Specific BXD strains demonstrate distinct motor learning impairments relevant to human DCD.
• Rab3a warrants further investigation as a potential genetic contributor to DCD, despite lacking nonsynonymous polymorphisms in this study.