Decreased Expression of Synaptophysin 1 (SYP1 Major Synaptic Vesicle Protein p38) and Contactin 6 (CNTN6/NB3) in the Cerebellar Vermis of reln Haplodeficient Mice.

Reeler heterozygous mice (reln) are seemingly normal but haplodeficient in reln, a gene implicated in autism. Structural/neurochemical alterations in the reln brain are subtle and difficult to demonstrate. Therefore, the usefulness of these mice in translational research is still debated. As evidence implicated several synapse-related genes in autism and the cerebellar vermis is structurally altered in the condition, we have investigated the expression of synaptophysin 1 (SYP1) and contactin 6 (CNTN6) within the vermis of reln mice. Semi-thin plastic sections of the vermis from adult mice of both sexes and different genotypes (reln and reln) were processed with an indirect immunofluorescence protocol. Immunofluorescence was quantified on binary images and statistically analyzed. Reln males displayed a statistically significant reduction of 11.89% in the expression of SYP1 compared to sex-matched wild-type animals, whereas no differences were observed between reln and reln females. In reln male mice, reductions were particularly evident in the molecular layer: 10.23% less SYP1 than reln males and 5.84% < reln females. In reln females, decrease was 9.84% versus reln males and 5.43% versus reln females. Both reln males and females showed a stronger decrease in CNTN6 expression throughout all the three cortical layers of the vermis: 17-23% in the granular layer, 24-26% in the Purkinje cell layer, and 9-14% in the molecular layer. Altogether, decrease of vermian SYP1 and CNTN6 in reln mice displayed patterns compatible with the structural modifications of the autistic cerebellum. Therefore, these mice may be a good model in translational studies.