Modeling the quantitative nature of neurodevelopmental disorders using Collaborative Cross mice

Area of Science:

• Genetics
• Neuroscience
• Animal Models

Background:

• Neurodevelopmental disorders (NDD) animal models often use single genetic mutations, contrasting with human genetics where Autism Spectrum Disorder (ASD) involves multiple genetic factors.
• Translational research in NDD requires animal models that can quantitatively assess genetic insults across varied genetic backgrounds.

Purpose of the Study:

• To investigate the quantitative genetic architecture of NDD-related behavioral phenotypes using a novel mouse genetic reference population.
• To identify suitable behavioral phenotypes for quantitative studies in NDD animal models.

Main Methods:

• Utilized the Collaborative Cross (CC), a genetically diverse mouse population.
• Assessed various behavioral phenotypes, including social recognition, grooming, digging, locomotor activity, and stereotyped exploratory patterns.

Main Results:

• Social recognition and grooming phenotypes showed limited heritability and were insufficient for quantitative NDD studies.
• Digging, locomotor activity, and stereotyped exploration exhibited continuous distributions and mapped to quantitative trait loci relevant to human NDD phenotypes.

Conclusions:

• The CC mouse model offers a powerful platform to advance NDD research beyond single-gene, single-background designs.
• Specific behavioral phenotypes like digging and activity are more amenable to quantifying genetic effects in NDD across diverse genetic backgrounds.