Behavioral and gene expression analyses in heterozygous XBP1 knockout mice: Possible contribution of chromosome 11qA1 locus to prepulse inhibition

The Xbp1 gene, located on chromosome 11qA1 in Mus musculus, encodes a key transcription factor in the endoplasmic reticulum stress response pathway. XBP1 play a role in brain development and implicated in pathogenesis of neurodegenerative and psychiatric diseases. To evaluate the role of Xbp1 in behavioral phenotypes, we subjected heterozygous Xbp1 knockout (Xbp1+/−) mice to a battery of behavioral tests. Xbp1+/− mice showed enhanced prepulse inhibition (PPI). We also examined gene expression profiles in frontal cortex and hippocampus of Xbp1+/− mice to investigate the molecular basis that could underlie behavioral phenotypes. Gene expression analysis showed that several genes located on chromosome 11qA1 were differentially expressed. Among them, Uqcr10 and Nipsnap1 were strongly up-regulated. Significant up-regulation of these genes in 129S compared with BALB/c as well as higher PPI in 129S than BALB/c was previously reported. The ES cells used to generation of XBP1 knockout mice were derived from 129S and the founder was backcrossed with BALB/c. Thus, these findings would be accounted for by 129S-derived chromosomal region flanking Xbp1. These results support the contribution of chromosome 11qA1 locus to the amount of PPI. Uqcr10 and Nipsnap1 are good candidate genes that could impact PPI.