ENDOGENOUS RETROVIRUS EXPRESSION IN TWO MOUSE MODELS OF AUTISM SPECTRUM DISORDERS.

Abstract

Background: Mobile retroelements such as Human Endogenous Retrovirus (HERV) have been implicated in complex diseases with multifactorial etiology, including neuropsychiatric disorders. We demonstrated that in peripheral blood mononuclear cells (PBMCs) from ASD patients, specific HERV show a distinctive expression profile compared to healthy controls. Aims: We evaluated the expression profile of different murine ERV families in two validated mouse models of ASD. Methods: The ASD models selected were i) the CD-1 outbred mice prenatally exposed to valproic acid (VPA, 500/mg/kg/bw) by injection of a single dose at gestational day 12.5 and ii) the inbred mouse line BTBR T+tf/J (BTBR) that shows behavioural abnormalities analogous to the core ASD symptoms. In parallel with the behavioural analysis, we quantified several MERV families from blood and brain samples at different postnatal days (1, 7, 23) with Real-time PCR. Results: VPA mice showed a delay of neonatal motor patterns and cognitive deficit as adults. In both blood and brain samples relative expression of MERV families was higher in VPA treated than in controls at all times of observation. The same enhanced expression profile of MERV was found in the BTBR line. Conclusions: Data obtained from blood and brain samples from the VPA and the BTBR mouse model are in agreement with what previously described in autistic children. Interestingly the MERV expression profile observed in brain samples from ASD mice parallel the one in blood samples. The high levels of expression found in brain support a role for MERV activation in atypical neurodevelopment