Abstract
The P2RX7 gene has been linked to various neuropsychiatric disorders. In particular, the SNP rs2230912, which results in a glutamine-to-arginine substitution at position 460, has repeatedly been associated with mood disorders. Although this SNP per se does not affect receptor function, it tags a gain-of-function haplotype that has been shown to significantly enhance receptor activity. BAC-transgenic P2X7-reporter mice have proven to be valuable tools for monitoring P2X7 expression. Here, we exploited their capacity to simultaneously overexpress the receptor, thereby serving as gain-of-function models to assess the behavioral consequences of elevated P2X7 levels. We used the two currently available transgenic P2X7 reporter lines (sEGFP and P2X7-EGFP), which differ in their expression pattern, degree of overexpression, and co-expression of the neighbouring P2rx4 gene. Male sEGFP and P2X7-EGFP mice showed no alterations in general activity or in measures of anxiety-related or stress-coping behavior compared to their wild-type littermates. Only male P2X7-EGFP mice exhibited slightly delayed locomotor habituation to a novel environment. To what extent higher expression levels reflect enhanced receptor activity, as conveyed by the disease-associated gain-of-function haplotype, requires further investigation. Overall, these results indicate that P2X7 overexpression—whether at endogenous or ectopic sites, or in conjunction with P2X4—is not sufficient to substantially alter behavior of individually housed male mice under baseline conditions.