Hippocampal gene expression profiling across eight mouse inbred strains: towards understanding the molecular basis for behaviour

Abstract

Mouse inbred strains differ in many aspects of their phenotypes, and it is known that gene expression does so too. This gives us an opportunity to isolate the genetic aspect of variation in expression and compare it to other phenotypic variables. We have investigated these issues using an eight-strain expression profile comparison with four replicates per strain on Affymetrix MGU74av2 GeneChips focusing on one well-defined brain tissue (the hippocampus). We identified substantial strain-specific variation in hippocampal gene expression, with more than two hundred genes showing strain differences by a very conservative criterion. Many such genetically driven differences in gene expression are likely to result in functional differences including differences in behaviour. A large panel of inbred strains could be used to identify genes functionally involved in particular phenotypes, similar to genetic correlation. The genetic correlation between expression profiles and function is potentially very powerful, especially given the current large-scale generation of phenotypic data on multiple strains (the Mouse Phenome Project). As an example, the strongest genetic correlation between more than 200 probe sets showing significant differences among our eight inbred strains and a ranking of these strains by aggression phenotype was found for Comt, a gene known to be involved in aggression.

The Catechol-O-Methyltransferase Polymorphism: Relations to the Tonic–Phasic Dopamine Hypothesis and Neuropsychiatric Phenotypes

“…This expectation is supported by the observation that COMT knockout mice exhibited elevated aggressive behavior, albeit this effect was limited to males (Gogos et al, 1998). Furthermore, in male mice, the more aggressive inbred strains had lower COMT expression levels in the hippocampus than the less aggressive strains (Fernandes et al, 2004).…”

Rodent models of focal stroke: Size, mechanism, and purpose

“…Thus, the mechanism for this interstrain difference in ischemic cell death remains to be determined. However, mouse strains have differences in many gene systems, including those related to cytokine and major histocompatibility complex expression, glial reactivity, and intracellular protein processing 73,79 that may contribute to differential sensitivity to ischemic cell death. An important point of this variability is that principles of cell death or neuroprotection derived from a single mouse strain should be replicated in additional strains before they are considered as generalized fact.…”

Molecular Identification and Physiological Roles of Parotid Acinar Cell Maxi-K Channels

“…Refs. [21][22][23][24][25], and the reduced secretion rate in these back-crossed animals serves to emphasize that these double-null animals must be compared with wild-type animals of the appropriate background. Shown in Fig.…”