Mutant Mice and Neuroscience: Recommendations Concerning Genetic Background

Banbury Conference on Genetic Background in Mice* identity of the genetic elements governing these other factors (modifiers) is usually unknown, it is important to keep them constant when evaluating the impact of a Mouse mutants derived by targeted mutagenesis in em-mutation. Only if the same genetic background is used bryonic stem (ES) cells offer many advantages to the across experiments can differences between the pheno-study of the molecular and cellular mechanisms underly-types obtained be ascribed to the mutations rather than ing behaviors such as learning and memory, circadian to different genetic backgrounds. Adoption of a com-rhythms, motor coordination, and aggression, as well mon genetic background does not preclude comparison as other neuroscience research areas such as brain of the effects of a given mutation in different back-development. The beginning of any new field, however, grounds. is often marked by a period in which key issues are Genetic background can be used as a tool in the debated, and as a consequence the approach is sharp-analysis of a mutation (e.g., quantitative trait loci analy-ened and focused. Theoretical and practical issues re-sis and enhancer/suppressor screens; Takahashi et al., lated to the impact of genetic background on the analy-1994). By placing the same mutation in different genetic sis of mutant mice have been a central topic of backgrounds, it is possible to study facets of gene func-Additionally, powerful new mapping and cloning strate-Analysis of the literature reveals that there is no consen-gies may allow the identification of modifiers from differ-sus on the nature of appropriate controls for genetic ent backgrounds (Dietrich et al., 1993; Gould et al., background. This report summarizes a recent Banbury 1996). Genetic interactions between a mutation and the workshop held in Cold Spring Harbor, New York, on genetic background may account for the variable pene-December 8–11, 1996, to discuss these issues in an trance of human genetic diseases, and it is important effort to come to a consensus within the field. The rec-to study and understand the nature of these interactions. ommendations that follow reflect the need for rigorously Most targeting experiments to date have relied on controlling the genetic background of experimental ani-the use of ES cells derived from substrain 129 mice. mals, and the practical issues surrounding the imple-However, the 129 substrains are a complex collection mentation of the appropriate controls. of various backgrounds, and so ES cells derived from Three principles emerged from our meeting. First, …