Impaired recognition memory in male mice with a supernumerary X chromosome

Several aberrant chromosomal constellations are known in men. or 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 (XXY*) 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 XXY* 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 C57B1/6 wild type mice carrying a normal Y chromosome, which provided a valid control group. All mice appeared healthy. XXY* mice did not differ from their wild type littermates with respect to locomotion. exploration and anxiety-related behavior. XXY* 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 XXY* mouse model affect brain function, in particular those regions responsible for cognition and learning behavior. (C) 2008 Elsevier Inc. All rights reserved.