Affiliations
Distinguished Research Professor, Integrative Biology and Physiology
Member, Brain Research Institute
Research Interests
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.
Publications
A selected list of publications:
Umar Soban, Cunningham Christine M, Itoh Yuichiro, Moazeni Shayan, Vaillancourt Mylene, Sarji Shervin, Centala Alex, Arnold Arthur P, Eghbali Mansoureh The Y Chromosome Plays a Protective Role in Experimental Hypoxic Pulmonary Hypertension American journal of respiratory and critical care medicine, 2018; 197(7): 952-955.
McCarthy Margaret M, Woolley Catherine S, Arnold Arthur P Incorporating sex as a biological variable in neuroscience: what do we gain? Nature reviews. Neuroscience, 2017; 18(12): 707-708.
Mauvais-Jarvis Franck, Arnold Arthur P, Reue Karen A Guide for the Design of Pre-clinical Studies on Sex Differences in Metabolism Cell metabolism, 2017; 25(6): 1216-1230.
Arnold Arthur P, Cassis Lisa A, Eghbali Mansoureh, Reue Karen, Sandberg Kathryn Sex Hormones and Sex Chromosomes Cause Sex Differences in the Development of Cardiovascular Diseases Arteriosclerosis, thrombosis, and vascular biology, 2017; 37(5): 746-756.
Arnold Arthur P Y chromosome’s roles in sex differences in disease Proceedings of the National Academy of Sciences of the United States of America, 2017; 114(15): 3787-3789.
Arnold Arthur P A general theory of sexual differentiation Journal of neuroscience research, 2017; 95(1-2): 291-300.
Miller Leah R, Marks Cheryl, Becker Jill B, Hurn Patricia D, Chen Wei-Jung, Woodruff Teresa, McCarthy Margaret M, Sohrabji Farida, Schiebinger Londa, Wetherington Cora Lee, Makris Susan, Arnold Arthur P, Einstein Gillian, Miller Virginia M, Sandberg Kathryn, Maier Susan, Cornelison Terri L, Clayton Janine A Considering sex as a biological variable in preclinical research FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2017; 31(1): 29-34.
Link Jenny C, Hasin-Brumshtein Yehudit, Cantor Rita M, Chen Xuqi, Arnold Arthur P, Lusis Aldons J, Reue Karen Diet, gonadal sex, and sex chromosome complement influence white adipose tissue miRNA expression BMC genomics, 2017; 18(1): 89.
Maric-Bilkan Christine, Arnold Arthur P, Taylor Doris A, Dwinell Melinda, Howlett Susan E, Wenger Nanette, Reckelhoff Jane F, Sandberg Kathryn, Churchill Gary, Levin Ellis, Lundberg Martha S Report of the National Heart, Lung, and Blood Institute Working Group on Sex Differences Research in Cardiovascular Disease: Scientific Questions and Challenges Hypertension (Dallas, Tex. : 1979), 2016; 67(5): 802-7.
Arnold Arthur P, Reue Karen, Eghbali Mansoureh, Vilain Eric, Chen Xuqi, Ghahramani Negar, Itoh Yuichiro, Li Jingyuan, Link Jenny C, Ngun Tuck, Williams-Burris Shayna M The importance of having two X chromosomes Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2016; 371(1688): 20150113.
Burgoyne Paul S, Arnold Arthur P A primer on the use of mouse models for identifying direct sex chromosome effects that cause sex differences in non-gonadal tissues Biology of sex differences, 2016; 7(1): 68.
Link Jenny C, Chen Xuqi, Prien Christopher, Borja Mark S, Hammerson Bradley, Oda Michael N, Arnold Arthur P, Reue Karen Increased high-density lipoprotein cholesterol levels in mice with XX versus XY sex chromosomes Arteriosclerosis, thrombosis, and vascular biology, 2015; 35(8): 1778-86.
Holásková Ida, Franko Jennifer, Goodman Robert L, Arnold Arthur P, Schafer Rosana The XX Sex Chromosome Complement is Required in Male and Female Mice for Enhancement of Immunity Induced by Exposure to 3,4-Dichloropropionanilide American journal of reproductive immunology (New York, N.Y. : 1989), 2015; 74(2): 136-47.
Itoh Yuichiro, Mackie Ryan, Kampf Kathy, Domadia Shelly, Brown Judith D, O’Neill Rachel, Arnold Arthur P Four core genotypes mouse model: localization of the Sry transgene and bioassay for testicular hormone levels BMC research notes, 2015; 8(8): 69.
Chen Xuqi, Wang Lixin, Loh Dawn H, Colwell Christopher S, Taché Yvette, Reue Karen, Arnold Arthur P Sex differences in diurnal rhythms of food intake in mice caused by gonadal hormones and complement of sex chromosomes Hormones and behavior, 2015; 75(8): 55-63.
Itoh Yuichiro, Arnold Arthur P Are females more variable than males in gene expression? Meta-analysis of microarray datasets Biology of sex differences, 2015; 6(1688): 18.
Manwani Bharti, Bentivegna Kathryn, Benashski Sharon E, Venna Venugopal Reddy, Xu Yan, Arnold Arthur P, McCullough Louise D Sex differences in ischemic stroke sensitivity are influenced by gonadal hormones, not by sex chromosome complement Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2015; 35(2): 221-9.
Itoh Yuichiro, Arnold Arthur P X chromosome regulation of autosomal gene expression in bovine blastocysts Chromosoma, 2014; 123(5): 481-9.
Arnold Arthur P Conceptual frameworks and mouse models for studying sex differences in physiology and disease: why compensation changes the game Experimental neurology, 2014; 259(5): 2-9.
Ngun Tuck C, Ghahramani Negar M, Creek Michelle M, Williams-Burris Shayna M, Barseghyan Hayk, Itoh Yuichiro, Sánchez Francisco J, McClusky Rebecca, Sinsheimer Janet S, Arnold Arthur P, Vilain Eric Feminized behavior and brain gene expression in a novel mouse model of Klinefelter Syndrome Archives of sexual behavior, 2014; 43(6): 1043-57.
Seu E, Groman S M, Arnold A P, Jentsch J D Sex chromosome complement influences operant responding for a palatable food in mice Genes, brain, and behavior, 2014; 13(6): 527-34.
Li Jingyuan, Chen Xuqi, McClusky Rebecca, Ruiz-Sundstrom Maureen, Itoh Yuichiro, Umar Soban, Arnold Arthur P, Eghbali Mansoureh The number of X chromosomes influences protection from cardiac ischaemia/reperfusion injury in mice: one X is better than two Cardiovascular research, 2014; 102(3): 375-84.
Ghahramani Negar M, Ngun Tuck C, Chen Pao-Yang, Tian Yuan, Krishnan Sangitha, Muir Stephanie, Rubbi Liudmilla, Arnold Arthur P, de Vries Geert J, Forger Nancy G, Pellegrini Matteo, Vilain Eric The effects of perinatal testosterone exposure on the DNA methylome of the mouse brain are late-emerging Biology of sex differences, 2014; 5(7): 8.
Du Sienmi, Itoh Noriko, Askarinam Sahar, Hill Haley, Arnold Arthur P, Voskuhl Rhonda R XY sex chromosome complement, compared with XX, in the CNS confers greater neurodegeneration during experimental autoimmune encephalomyelitis Proceedings of the National Academy of Sciences of the United States of America, 2014; 111(7): 2806-11.
Arnold Arthur P, Chen Xuqi, Link Jenny C, Itoh Yuichiro, Reue Karen Cell-autonomous sex determination outside of the gonad Developmental dynamics : an official publication of the American Association of Anatomists, 2013; 242(4): 371-9.
Kuljis Dika A, Loh Dawn H, Truong Danny, Vosko Andrew M, Ong Margaret L, McClusky Rebecca, Arnold Arthur P, Colwell Christopher S Gonadal- and sex-chromosome-dependent sex differences in the circadian system Endocrinology, 2013; 154(4): 1501-12.
Link Jenny C, Chen Xuqi, Arnold Arthur P, Reue Karen Metabolic impact of sex chromosomes Adipocyte, 2013; 2(2): 74-9.
Chen Xuqi, McClusky Rebecca, Itoh Yuichiro, Reue Karen, Arnold Arthur P X and Y chromosome complement influence adiposity and metabolism in mice Endocrinology, 2013; 154(3): 1092-104.
Chen Xuqi, Williams-Burris Shayna M, McClusky Rebecca, Ngun Tuck C, Ghahramani Negar, Barseghyan Hayk, Reue Karen, Vilain Eric, Arnold Arthur P The Sex Chromosome Trisomy mouse model of XXY and XYY: metabolism and motor performance Biology of sex differences, 2013; 4(1): 15.
Drnevich Jenny, Replogle Kirstin L, Lovell Peter, Hahn Thomas P, Johnson Frank, Mast Thomas G, Nordeen Ernest, Nordeen Kathy, Strand Christy, London Sarah E, Mukai Motoko, Wingfield John C, Arnold Arthur P, Ball Gregory F, Brenowitz Eliot A, Wade Juli, Mello Claudio V, Clayton David F Impact of experience-dependent and -independent factors on gene expression in songbird brain Proceedings of the National Academy of Sciences of the United States of America, 2012; 109 Suppl 2(3): 17245-52.
Arnold Arthur P, Lusis Aldons J Understanding the sexome: measuring and reporting sex differences in gene systems Endocrinology, 2012; 153(6): 2551-5.
McCarthy Margaret M, Arnold Arthur P, Ball Gregory F, Blaustein Jeffrey D, De Vries Geert J Sex differences in the brain: the not so inconvenient truth The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012; 32(7): 2241-7.
Arnold Arthur P The end of gonad-centric sex determination in mammals Trends in genetics : TIG, 2012; 28(2): 55-61.
Chen Xuqi, McClusky Rebecca, Chen Jenny, Beaven Simon W, Tontonoz Peter, Arnold Arthur P, Reue Karen The number of x chromosomes causes sex differences in adiposity in mice PLoS genetics, 2012; 8(5): e1002709.
Arnold Arthur P, Chen Xuqi, Itoh Yuichiro What a difference an X or Y makes: sex chromosomes, gene dose, and epigenetics in sexual differentiation Handbook of experimental pharmacology, 2012; 28(214): 67-88.
Itoh Yuichiro, Kampf Kathy, Arnold Arthur P Possible differences in the two Z chromosomes in male chickens and evolution of MHM sequences in Galliformes Chromosoma, 2011; 120(6): 587-98.
Robinson Dionne P, Huber Sally A, Moussawi Mohamad, Roberts Brian, Teuscher Cory, Watkins Rebecca, Arnold Arthur P, Klein Sabra L Sex chromosome complement contributes to sex differences in coxsackievirus B3 but not influenza A virus pathogenesis Biology of sex differences, 2011; 2(6): 8.
Arnold AP, Itoh Y, Melamed E A bird’s eye view of sex chromosome dosage compensation, Annual Review of Genomics and Human Genetics, 2008; in press: .
*Gioiosa L, *Chen X (co-first authors), Watkins R, Klanfer N, Bryant CD, Evans CJ, Arnold AP Sex chromosome complement affects nociception in tests of actue and chronic exposure to morphine in mice, Hormones and Behavior, 2008; 54: 124-130.
Chen X, Watkins R, Delot E, Releine R, Schiestl RH, Burgoyne PS, Arnold AP Sex difference in neural tube defects in p53-null mice is caused by differences in the complement of X not Y genes, Developmental Neurobiology, 2008; 68: 265-273.
*Itoh Y, *Melamed E (*co-first authors), Yang X, Kampf K, Wang S, Yehya N, Van Nas A, Replogle K, Band MR, Clayton DF, Schadt EE, Lusis AJ, Arnold AP Dosage compensation is less effective in birds than in mammals Journal of Biology, 2007; 6: 2.
Melamed E, Arnold AP Regional differences in dosage compensation on the chicken Z chromosome, Genome Biology, 2007; 8: R202.
Quinn JJ, Hitchcott PK, Umeda EA, Arnold AP, Taylor JR Sex chromosome complement determines habit formation, Nature Neuroscience, 2007; 10: 1398-1400.
Gatewood JD, Wills A, Shetty S, Xu J, Arnold AP, Burgoyne PS, Rissman EF. Sex chromosome complement and gonadal sex influence aggressive and parental behaviors in mice, Journal of Neuroscience, 2006; 26: 2335-2342.
Palaszynski KM, Smith DL, Burgoyne PS, Arnold AP, Voskuhl RR A yin-yang effect between sex chromosomes and sex hormones on the immune response, Endocrinology, 2005; 146: 3280-3285.
Chen X, Agate RJ, Itoh Y, Arnold AP Sexually dimorphic expression of trkB, a Z-linked gene, in early posthatch zebra finch brain, Proceedings of the National Academy of Sciences USA , 2005; 102: 7730-7735.
Arnold AP Sex chromosomes and brain gender Nature Reviews Neuroscience , 2004; 5(9): 701-8.
Arnold, AP Burgoyne, PS Are XX and XY brain cells intrinsically different? Trends in endocrinology and metabolism: TEM. , 2004; 15(1): 6-11.
Agate RJ, Grisham W, Wade J, Mann S, Wingfield J, Schanen C, Palotie A, Arnold AP Neural not gonadal origin of brain sex differences in a gynandromorphic finch, Proceedings of the National Academy of Sciences USA, 2003; 100: 4873-4878.
Carruth LC, Reisert I, Arnold AP Direct effect of sex chromosome genes on brain sexual differentiation, Nature Neuroscience , 2002; 5: 933-934.
De Vries GJ, Rissman EF, Simerly RB, Yang L-Y , Scordalakes EM, Auger C, Swain A, Lovell-Badge R, Burgoyne PS, Arnold AP Sex chromosome effects on the induction of sexually dimorphic neural and behavioral development, Journal of Neuroscience, 2002; 22: 9005-9014.