title: Feminized behavior and brain gene expression in a novel mouse model of Klinefelter Syndrome.
abstract: Klinefelter Syndrome (KS) is the most common sex chromosome aneuploidy in men and is characterized by the presence of an additional X chromosome (XXY). In some Klinefelter males, certain traits may be feminized or shifted from the male-typical pattern towards a more female-typical one. Among them might be partner choice, one of the most sexually dimorphic traits in the animal kingdom. We investigated the extent of feminization in XXY male mice (XXYM) in partner preference and gene expression in the bed nucleus of the stria terminalis/preoptic area and the striatum in mice from the Sex Chromosome Trisomy model. We tested for partner preference using a three-chambered apparatus in which the test mouse was free to choose between stimulus animals of either sex. We found that partner preference in XXYM was feminized. These differences were likely due to interactions of the additional X chromosome with the Y. We also discovered genes that differed in expression in XXYM versus XYM. Some of these genes are feminized in their expression pattern. Lastly, we also identified genes that differed only between XXYM versus XYM and not XXM versus XYM. Genes that are both feminized and unique to XXYM versus XYM represent strong candidates for dissecting the molecular pathways responsible for phenotypes present in KS/XXYM but not XXM. In sum, our results demonstrated that investigating behavioral and molecular feminization in XXY males can provide crucial information about the pathophysiology of KS and may aid our understanding of sex differences in brain and behavior.
authors.affiliation: Department of Human Genetics, David Geffen School of Medicine at University of California, 695 Charles E. Young Dr. S, Gonda 5506, MC 708822, Los Angeles, CA, 90095-7088, USA.
authors.forename: Tuck C
authors.initials: TC
authors.lastname: Ngun
authors.forename: Negar M
authors.initials: NM
authors.lastname: Ghahramani
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Creek
authors.forename: Shayna M
authors.initials: SM
authors.lastname: Williams-Burris
authors.forename: Hayk
authors.initials: H
authors.lastname: Barseghyan
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Itoh
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Sánchez
authors.forename: Rebecca
authors.initials: R
authors.lastname: McClusky
authors.forename: Janet S
authors.initials: JS
authors.lastname: Sinsheimer
authors.forename: Arthur P
authors.initials: AP
authors.lastname: Arnold
authors.forename: Eric
authors.initials: E
authors.lastname: Vilain
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D001923:Brain Chemistry; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D007713:Klinefelter Syndrome / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D012737:Sex Factors; D012726:Sexual Behavior, Animal / Q000502:physiology*