Distinct Alteration of Gene Expression Programs in the Small Intestine of Male and Female Mice in Response to Ablation of Intestinal Fabp Genes

Abstract

Fatty acid-binding proteins (Fabps) make up a family of widely distributed cytoplasmic lipid-binding proteins. The small intestine contains three predominant Fabp species, Fabp1, Fabp2, and Fabp6. Our previous studies showed that Fabp2 and Fabp6 gene-disrupted mice exhibited sexually dimorphic phenotypes. In this study, we carried out a systematic comparative analysis of the small intestinal transcriptomes of 10 week-old wild-type (WT) and Fabp gene-disrupted male and female mice. We found that the small intestinal transcriptome of male and female mice showed key differences in the gene expression profiles that affect major biological processes. The deletion of specific Fabp genes induced unique and sex-specific changes in the gene expression program, although some differentially expressed genes in certain genotypes were common to both sexes. Functional annotation and interaction network analyses revealed that the number and type of affected pathways, as well as the sets of interacting nodes in each of the Fabp genotypes, are partitioned by sex. To our knowledge, this is the first time that sex differences were identified and categorized at the transcriptome level in mice lacking different intestinal Fabps. The distinctive transcriptome profiles of WT male and female small intestine may predetermine the nature of transcriptional reprogramming that manifests as sexually dimorphic responses to the ablation of intestinal Fabp genes.