The importance of having two X chromosomes

Arthur P Arnold; Karen Reue; Mansoureh Eghbali; Eric Vilain; Xuqi Chen; Negar Ghahramani; Yuichiro Itoh; Jingyuan Li; Jenny C Link; Tuck Ngun; Shayna M Williams-Burris

doi:10.1098/rstb.2015.0113

The importance of having two X chromosomes

Philos Trans R Soc Lond B Biol Sci. 2016 Feb 19;371(1688):20150113. doi: 10.1098/rstb.2015.0113. Epub 2016 Feb 1.

Authors

Affiliations

¹ Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA Laboratory of Neuroendocrinology, UCLA Brain Research Institute, Los Angeles, CA, USA [email protected].
² Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
³ Department of Anesthesiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
⁴ Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
⁵ Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA Laboratory of Neuroendocrinology, UCLA Brain Research Institute, Los Angeles, CA, USA.
⁶ Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA Laboratory of Neuroendocrinology, UCLA Brain Research Institute, Los Angeles, CA, USA.
⁷ Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA Interdepartmental Program for Neuroscience, University of California, Los Angeles, Los Angeles, CA, USA Laboratory of Neuroendocrinology, UCLA Brain Research Institute, Los Angeles, CA, USA.

Abstract

Historically, it was thought that the number of X chromosomes plays little role in causing sex differences in traits. Recently, selected mouse models have been used increasingly to compare mice with the same type of gonad but with one versus two copies of the X chromosome. Study of these models demonstrates that mice with one X chromosome can be strikingly different from those with two X chromosomes, when the differences are not attributable to confounding group differences in gonadal hormones. The number of X chromosomes affects adiposity and metabolic disease, cardiovascular ischaemia/reperfusion injury and behaviour. The effects of X chromosome number are likely the result of inherent differences in expression of X genes that escape inactivation, and are therefore expressed from both X chromosomes in XX mice, resulting in a higher level of expression when two X chromosomes are present. The effects of X chromosome number contribute to sex differences in disease phenotypes, and may explain some features of X chromosome aneuploidies such as in Turner and Klinefelter syndromes.

Keywords: Klinefelter; X chromosome; ischaemia; obesity; sex differences; sexual differentiation.

Publication types

Research Support, N.I.H., Extramural
Review

MeSH terms

Animals
Female
Gene Expression Regulation / physiology
Genotype
Gonadal Steroid Hormones / metabolism
Male
Sex Factors
X Chromosome / genetics*

Substances

Gonadal Steroid Hormones

Abstract

Publication types

MeSH terms

Substances

Grants and funding