The de novo Autism Spectrum Disorder RELN R2290C Mutation Reduces Reelin Secretion and Increases Protein Disulfide Isomerase Expression

To determine if changes in Protein Disulfide Isomerase (PDIA1) expression in mice with a null Reelin allele were caused by accumulation of intracellular Reelin or were an effect of reduced Reelin protein, we examined expression of PDIA1 and other stress markers in heterozygous RELN +/- null allele mice. The levels of PDIA1 as well as PERK, BIP, phospho-eIF2alpha and total eIF2alpha were unchanged between wild-type and RELN +/- null allele mice. This suggested that there are phenotypic differences in the cerebella between mice that carry a RELN allele that fails to produce a protein (null allele) and those that make a protein that fails to be secreted (Orl allele). Each of the three major ER stress pathways ultimately leads to changes in gene transcription. Thus, we compared wild-type and heterozygous RELN Orl +/- mice cerebellum by RNAseq. Analysis was performed on 3 heterozygous (HET) and 3 wild-type (WT) cerebella, obtained from 6-week old male mice. Overall design: Comaprison of gene expression in the cerebellum of Reelin heterozygous null mice and wildtype mice using RNA-seq