Designer mutants for behavioral genetics

One way of investigating the role of a gene or genomic locus in modulating a behavioral response is to examine those behavioral responses when that gene or genomic locus is not working properly due to a complete loss of function (null) or a partial loss of function (hypomorph) or a stronger or new role (gain-of-function). With recent advances in targeted gene editing, it is now possible to create null alleles or gene variants that are expected to have some altered function (for review, see Lee et al., 2016; Simone et al., 2018) and subsequently determine how those genetic changes impact an organism's ability to respond to stimuli in various behavioral assessments. When establishing a new edited allele in the genome for further analysis on behavioral responses, there are some important key considerations. First, will the editing method employed efficiently produce the desired change to the genome like a complete null or partial loss-of-function of the gene of interest? Second, how do we limit the impact of off-target (undesired alleles created by the editing strategy) or bystander (background alleles) mutations that may modify the behavior being observed by adhering to standard genetic principles? Third, how do we maintain genetically diverse stock without genetic bottleneck effects while deriving and establishing a desired mutant variant? This chapter briefly surveys various methods of targeted mutagenesis using programmable endonucleases and discusses ideal genetic practices that will aid in determining whether the programmed change is a key regulator of the observed phenotype or a result of off-target or bystander influences.