The Collaborative Cross Mouse A Powerful Tool for Studying Complex Genetic Conditions of Neurogenesis and Brain Development
Abstract
Diji Kuriakose and Zhicheng Xiao
Neurodegenerative disorders (NDD), like Alzheimer’s disease (AD), impose a large health and socio-economic burden. AD affected 50 million people worldwide in 2019, and was the fifth leading cause of death for people over 65 years old. Despite the high prevalences of NDDs, very little is known about their underlying mechanisms and causes. Commonly occurring comorbidities and symptoms – such as cognitive impairment – overlap, complicating differential diagnosis. Recent studies have also noted large differences between the diagnostic outcomes associated with different genetic causes. In humans, multiple genetic variants are associated with neurogenesis and NDDs. Most research on NDDs uses animal models that focus on a single mutation in a fixed genetic background, providing inadequate heterogeneity and power to map genes linked to complex disease conditions. Therefore, it is imperative for NDD research to use next-generation animal models with greater genetic diversity. The Collaborative Cross (CC) mouse captures over 90% of the genetic diversity of the mouse species in a set of recombinant inbred lines to maximize genetic power. The CC model improves the outcomes of lab research: it enables population-based laboratory study, generates efficient and reproducible datasets, and allows researchers to identify multiple causative genetic factors for neurobehavioural traits. The convergence of all these characteristics will advance the translational value of laboratory research and create commercially viable, cost-effective clinical interventions.