Increased P2X7 level does not affect anxiety or stress-coping behavior in male mice

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.