Abstract

The objective of this study is to identify sex differentially expressed genes in bone using a mouse model of spontaneous fracture, sfx, which lacks the gene for L-gulonolactone oxidase (Gulo), a key enzyme in the ascorbic acid (AA) synthesis pathway. We first identified the genes that are differentially expressed in the femur between female and male in sfx mice. We then analyzed the potential gene network among those differentially expressed genes with whole genome expression profiles generated using spleens of female and male mice of a total of 67 BXD (C57BL/6J X DBA/2J) recombinant inbred (RI) and other strains. Our result indicated that there was a sex difference in the whole genome profiles in sfx mice as measured by the proportion of up- and downregulated genes. Several genes in the pathway of bone development are differentially expressed between the male and female of sfx mice. Comparison of gene network of up- and downregulated bone relevant genes also suggests a sex difference.

Highlights

  • In humans, gender difference in vitamin C (VC) requirement has been suggested by several studies [1,2,3]

  • Study on the 970 human skeletons from mass burials dating to the height of the famine in Kilkenny City [4] provided an opportunity to study the skeletal manifestations of scurvy—a disease that became widespread at this time due to the sudden lack of VC

  • In order to elucidate the molecular pathways among genes differentially expressed between female and male sfx mice, we examined the associations among those genes using gene expression profiles of spleen in BXD recombinant inbred (RI) strains

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Summary

Introduction

Gender difference in vitamin C (VC) requirement has been suggested by several studies [1,2,3]. VC is essential for the skeletal development. It is not clear whether the different VC requirement is due to the gender skeletal difference. Study on the 970 human skeletons from mass burials dating to the height of the famine in Kilkenny City [4] provided an opportunity to study the skeletal manifestations of scurvy—a disease that became widespread at this time due to the sudden lack of VC. The study provided evidence to support an investigation on the gender difference when lacking VC in humans. A sex difference has been evidenced [5, 6]

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