Copy number variants in two mouse models of affective disorders

In our lab we established two inbred mouse models to study the molecular underpinnings of psychiatric diseases like depression, anxiety disorders and pathological stress reactivity. Starting from a heterogeneous CD-1 outbred population, animals were bred for extremes in anxiety-related behavior and extremes in stress reactivity, respectively, following a strict inbreeding protocol. Both models were subjected to extensive studies regarding their behavioral, neuroendocrine, and genetic features. In an unbiased approach we are currently focusing on the discovery of copy number variants (CNVs) and their implications in the endophenotypes of these animals. Two array approaches were used to reveal regions of CNVs that differ between the extremes of the respective mouse lines (aCGH, NimbleGen; SNP-based invariant genomic probes, Jackson Laboratories). In total, we identified approximately 100 CNV regions ranging from around 10 kb to 7 Mb. To test the functional relevance of these CNVs, we associated changes in copy numbers with changes in gene expression. A simple correlation between gene dosage and gene expression could not be found in all cases. Furthermore, genomic loci, which were detected in association studies and therefore are of special interest in the context of these endophenotypes, were compared to the CNV data sets. Further studies to define the precise role of CNVs on gene expression remain to be conducted.