Effect of Zbtb33 gene knockout and bacterial lipopolysaccharide on home cage behavior in mice

Abstract

The Zbtb33 gene encodes the bimodal transcriptional repressor Kaiso, which causes epigenetic repression of genes by binding to methylated mCpG islets in the promoters of the genes. Despite the fact that Kaiso is intensively expressed in the central nervous system, its participation in the regulation of behavior is still poorly understood. Only the participation of Kaiso in the regulation of the behavioral response to emotional stress in the open field and forced swimming tests has been shown. The aim of this study is to elucidate the role that Kaiso plays in regulating daily activity, as well as the behavioral response to stimulation of nonspecific immunity. Experiments were performed on adult male mice with Zbtb33 gene knockout (KO) and animals of the C57BL/6 line (wild type, WT). All animals were 11 weeks old, weighed 26 ± 1 g and had SPF (specific pathogen free) status throughout the experiment. The animals of each genotype were divided into three weighted groups of 8 animals each. Initially, the daily dynamics of motor activity, sleep, food and water intake of intact animals was measured using the PhenoMaster software-hardware complex. The animals of each group were then injected with saline (control), 0.1 or 1.0 mg/kg of bacterial lipopolysaccharide (LPS) dissolved in saline, and again measured for their daily activity, food and water intake. Intact KO and WT mice did not differ in the average daily motor activity and sleep duration. However, intact KO mice were less active in the dark time, and also consumed less food and water as compared to intact WT animals. LPS at both doses suppressed motor activity, prolonged sleep duration and caused anorexia in mice of both genotypes. However, the effect of low dose of LPS (0.1 mg/kg) on the food and water intake was more pronounced in KO mice than in WT animals. The results shed light on the biological significance of the Kaiso gene and serve as a justification for the necessity of the normal functioning of this gene in natural populations.