Examination of the AVPR1a Microsatellites in Relation to Human Promoter Activity

Background: Autism is a neurodevelopmental disorder encompassing three core areas of behaviour: deficits in communication, deficits in social behaviours and the presence of restricted repetitive behaviours. The neuropeptide vasopressin has been implicated in the aetiology of autism. It has been shown through animal models to mediate social cognition, encompassing social memory formation, social recognition, and social motivation. These processes are impaired in autism. Through work in voles, a single functional microsatellite upstream from the arginine vasopressin receptor 1A (AVPR1a) was found to be associated with social behaviours (Hammock and Young 2001). In humans, three microsatellites are located in this region.

Objectives: We examined the effect of human microsatellite RS1 on the expression of AVPR1a using a reporter assay system.

Methods: Alleles were chosen based upon length of polymorphism repeat using a short and long repeat for each. Inserts contained the microsatellite repeat and the promoter region up to the start of transcription. Inserts for each length were cloned into the pGL3 basic vector (Promega, UK). Each construct was then tested in 2 different cell lines – CHO K1, and SH SY-5Y. Differences in the promoter activity between the different length repeats was then determined using a luciferase reporter assay system (Promega, UK).

Results: In both cell lines (CHO K1 and SH SY-5Y) no increases in relative expression levels compared to background were observed.

Conclusions: It is possible the microsatellite RS1 is inhibiting the promoter activity and further work will be performed to investigate this.