Klinefelter Syndrome is a common chromosomal abnormality of males who have two X chromosomes XXY, rather than one, XY. XXY males experience a variety of congenital developmental problems, including infertility, lower levels of androgens, increased risk for obesity and metabolic disease, increased risk for autoimmune diseases, and cognitive features including alterations in executive function and delayed language development. The long-term objectives of this project are to identify X chromosome genes that cause behavioral features of Klinefelter Syndrome, using novel mouse models. An overarching question is to separate the direct effects of X chromosome genes that cause Klinefelter Syndrome traits, from those caused by lower testosterone levels in XXY individuals. A novel mouse model produces XXY, XY, and XX mice that have either testes or ovaries, so that sex chromosomal effects can be identified that do not require testicular secretions, or occur when testicular secretions do not explain differences. Mice will be compared in a series of Klinefelter Syndrome-relevant behavioral measurements that assess executive functions, development of vocalizations, and partner preference. The expression levels of six specific X chromosome genes, which are the major candidates for causing the features of Klinefelter Syndrome, will be directly manipulated to assess which is/are likely the causal genes in the mouse model.
Klinefelter Syndrome is caused by a chromosomal abnormality, the presence of a second X chromosome in males. The proposed research aims to model the Syndrome in XXY mice, to identify the X genes that cause behavioral features related to Klinefelter Syndrome, which will catalyze better understanding and treatment of Klinefelter Syndrome.
| Arnold, Arthur P; Disteche, Christine M (2018) Sexual Inequality in the Cancer Cell. Cancer Res 78:5504-5505 |
| Umar, Soban; Cunningham, Christine M; Itoh, Yuichiro et al. (2018) The Y Chromosome Plays a Protective Role in Experimental Hypoxic Pulmonary Hypertension. Am J Respir Crit Care Med 197:952-955 |
| Dinarello, Charles Anthony (2018) An Interleukin-1 Signature in Breast Cancer Treated with Interleukin-1 Receptor Blockade: Implications for Treating Cytokine Release Syndrome of Checkpoint Inhibitors. Cancer Res 78:5200-5202 |
| Arnold, Arthur P; Cassis, Lisa A; Eghbali, Mansoureh et al. (2017) Sex Hormones and Sex Chromosomes Cause Sex Differences in the Development of Cardiovascular Diseases. Arterioscler Thromb Vasc Biol 37:746-756 |
| Miller, Leah R; Marks, Cheryl; Becker, Jill B et al. (2017) Considering sex as a biological variable in preclinical research. FASEB J 31:29-34 |
| Arnold, Arthur P (2017) Y chromosome's roles in sex differences in disease. Proc Natl Acad Sci U S A 114:3787-3789 |
| Mauvais-Jarvis, Franck; Arnold, Arthur P; Reue, Karen (2017) A Guide for the Design of Pre-clinical Studies on Sex Differences in Metabolism. Cell Metab 25:1216-1230 |
| McCarthy, Margaret M; Woolley, Catherine S; Arnold, Arthur P (2017) Incorporating sex as a biological variable in neuroscience: what do we gain? Nat Rev Neurosci 18:707-708 |
| Arnold, Arthur P (2017) A general theory of sexual differentiation. J Neurosci Res 95:291-300 |
| Arnold, Arthur P; Reue, Karen; Eghbali, Mansoureh et al. (2016) The importance of having two X chromosomes. Philos Trans R Soc Lond B Biol Sci 371:20150113 |
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