title: Impaired recognition memory in male mice with a supernumerary X chromosome.
abstract: Several aberrant chromosomal constellations are known in men. Of these the karyotype XXY (Klinefelter syndrome, KS) is the most common chromosomal disorder with a prevalence of about one in 800 live-born boys. KS is associated with hypogonadism and is suspected to cause variable physical, physiological and cognitive abnormalities. As a supernumerary X chromosome is also associated with infertility, sound animal models for KS are difficult to obtain. In this study, male mice with two X chromosomes (XX(Y*)) were derived from fathers carrying a structurally rearranged Y chromosome (Y*) that resulted in physical attachment of a part of the Y chromosome to one X. These animals display certain physiological features that resemble closely those of human KS and can also be utilized to study X chromosomal imbalance and cognition. Therefore 15 XX(Y*) males and 15 XY* controls were subjected to a battery of behavioral tests, including a general health check, analysis of spontaneous exploration and locomotor activity, measures for anxiety-related behavior and the "novel object task" to test memory performance. Physiologically, XY* males did not differ from C57Bl/6 wild type mice carrying a normal Y chromosome, which provided a valid control group. All mice appeared healthy. XX(Y*) mice did not differ from their wild type littermates with respect to locomotion, exploration and anxiety-related behavior. XX(Y*) male mice, however, exhibited no significant recognition memory performance in contrast with wild type XY* males that readily fulfilled a given task. These findings support the hypothesis that the presence of a supernumerary X in male mice influences cognitive abilities. We suggest that the altered endocrine state and/or changes in the dosage of X-linked genes in the XX(Y*) mouse model affect brain function, in particular those regions responsible for cognition and learning behavior.
authors.affiliation: Department of Behavioural Biology, University of Münster, Münster, Germany. ljohann@phenotyping.com
authors.forename: Lars
authors.initials: L
authors.lastname: Lewejohann
authors.forename: Oliver S
authors.initials: OS
authors.lastname: Damm
authors.forename: C Marc
authors.initials: CM
authors.lastname: Luetjens
authors.forename: Tuula
authors.initials: T
authors.lastname: Hämäläinen
authors.forename: Manuela
authors.initials: M
authors.lastname: Simoni
authors.forename: Eberhard
authors.initials: E
authors.lastname: Nieschlag
authors.forename: Jörg
authors.initials: J
authors.lastname: Gromoll
authors.forename: Joachim
authors.initials: J
authors.lastname: Wistuba