Abstract

Rodent Models of Neurodevelopmental Diseases to Improve Rigour and Reproducibility.

Author(s): Robert Wilsom

Research on rats is needed to increase our understanding of the genetic and environmental risk factors for neurodevelopmental
disorders (NDD). Concern is mounting about the number of challenging-to-replicate animal experiments that could cast doubt on the
validity of findings. Higher requirements have been set by funding organisations and academic journals in an effort to increase
repeatability in research. The "litter effect," which refers to the fact that mice from the same litter are phenotypically more similar to
one another than rodents from other litters of the same strain, is a significant source of variability in rodent research and is not addressed
by these guidelines. We demonstrate that the litter effect explains 30%–60% of the variability linked to traits that are frequently
examined, such as the brain, placenta, and body weight.
The vast majority of NDD studies focused on genetic risks, including mutant mouse studies, and environmental risks, such as air pollution
and valproic acid exposure, do not correct for litter effects or provide information on the number of litters used. This is despite efforts
to inform scientists about the significance of controlling for litter effects in previous publications. We provide recommendations for best
practises that can be used to lessen the effect of litter-to-litter variation and improve the rigour and repeatability of upcoming NDD studies
utilising rodent models.