〔Abstract〕 Objective To investigate the molecular changes of lanosterol synthase(LSS) gene dysfunction and cholesterol levels that may affect brain function. Methods The differentially expressed genes in LSS knockout(+/-) mice and WT C57 BL/6 mice were analyzed by RNA-SEQ,and the signal pathways involved in the differentially expressed genes were analyzed by KEGG enrichment. The differential genes were detected by real-time quantitative PCR and the protein expression of differential genes was detected by Western blot. Results By RNA-SEQ analysis, LSS(+/-) heterozygous knockout resulted in the difference of 320 genes in the mouse brain, including 145 up-regulated genes and 175 down-regulated genes.KEGG enrichment analysis showed that these differentially expressed genes involved in neural-activated receptor and ligand pathways, hippocampal signaling pathways and glutamate synaptic pathways.Real-time quantitative PCR showed that CCKBR and Htr5 b were up-regulated, respectively. Western blot results showed that CCKBR gene was highly expressed in the total protein of all brain tissues of LSS knockout(+/-) mice. Conclusion LSS heterozygotic knockout may affect brain function and animal behavior.