office: 1129 TLSB
research interests: Sex differences in the brain, neuroendocrinology, evolution and function of the sex chromosomes
We study the forces that differentiate male and female tissues. Sexual differentiation underlies sex differences in behavior, physiology, and susceptibility to disease. Our recent research on mice indicates that genes on the sex chromosomes, X and Y genes, are expressed differently in male and female cells and induce sex differences in non-gonadal tissues. These direct genetic actions interact with effects of gonadal hormones in the two sexes. Our goal is to identify X and Y genes that contribute to sex differences in tissue function and disease, and to understand the mechanisms of their action. We also study sex chromosome dosage compensation in birds. Males have two Z chromosomes but females have one. Birds have an ineffective mechanism of dosage compensation, which is not predicted from study of mammals and other XX/XY systems. We seek to understand the epigenetic modifications of the Z chromosome that regulate gene dosage, and the evolution of dosage compensation mechanisms.
Manwani B, Bentivegna K, Benashski SE, Venna VR, Yu Y, Arnold AP, McCullough LD, "Sex differences in ischemic stroke sensitivity are influenced by gonadal hormones, not by sex chromosome complement", Journal of Cerebral Blood Flow & Metabolism, 34 : 1-9 (2014) .
Ghahramani NM, Ngun TC, Chen P-Y, Tian Y, Krishnan S, Muir S, Rubbi L, Arnold AP, de Vries GJ, Forger NG, Pellegrini M, Vilain E, "The effects of perinatal testosterone exposure on the DNA methylome of the mouse brain are late-emerging", Biology of Sex Differences, 5 : 8-18 (2014) [link].
Ngun TC, Ghahramani NM, Creek MN, Williams-Burris SM, Barseghyan H, Itoh Y, Sanchez FJ, McClusky R, Sinsheimer JS, Arnold AP, Vilain, E, "Feminized behavior and brain gene expression in a novel mouse model of Klinefelter Syndrome", Archives of Sexual Behavior, 43 : 1043-1057 (2014) .
Seu E, Groman S, Arnold AP, Jentsch JD, "Sex chromosome complement influences operant responding for a palatable food in mice", Genes, Brain and Behavior, 13 : 527-534 (2014) .
Itoh Y, Arnold AP, "X chromosome regulation of autosomal gene expression in bovine blastocysts", Chromosoma, 123 : 481-489 (2014) .
Li J, Chen X, McClusky R, Ruiz-Sundstrom M, Itoh Y, Umar S, Arnold AP and Eghbali M, "The number of X chromosomes influences protection from cardiac ischemia/reperfusion injury in mice: One X is better than two", Cardiovascular Research, 102 : 375-384 (2014) .
Du S., Itoh N, Askarinama S, Hilla H, Arnold AP, Voskuhl RR, "XY sex chromosome complement, compared with XX, in the CNS confers greater neurodegenerative during experimental autoimmune encephalomyelitis", Proceedings of the National Academy of Sciences, USA, 111 : 2806-2811 (2014) .
Arnold AP, "Conceptual frameworks and mouse models for studying sex differences in physiology and disease: Why compensation changes the game", Experimental Neurology,, 259 : 2-9 (2014) .
Chen X*. Williams-Burris SM*, McClusky R, Ngun TC, Ghahramani N, Barseghyan H, Reue K, Vilain E, Arnold AP. (*equal authors), "The sex chromosome trisomy mouse model of XXY and XYY: Metabolism and motor performance", Biology of Sex Differences, 5 : 15- (2013) [link].
Kuljis DA, Loh DH, Truong D, Vosko AM, Ong ML, McClusky R, Arnold AP, Colwell CS, "Gonadal- and sex-chromosome-dependent sex differences in the circadian system", Endocrinology, 154 : 1501-1512 (2013) .