ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 OC5.9

Cognitive disabilities in the novel object task of male mice carrying a supernumerary X chromosome (41, XX*Y)

Joachim Wistuba1,2, Oliver Damm1,2, C Marc Luetjens1,2, Manuela Simoni1,2, Eberhard Nieschlag1,2 & Lars Lewejohann1,2

1Abteilung für Verhaltensbiologie und Otto Creutzfeldt Center, Münster, Germany; 2Institut für Reproduktionsmedizin, Münster, Germany.

Introduction: Several numerical chromosome abberations are known in men. Of those the karyotype XXY (Klinefelter syndrome KS) is the most common chromosomal disorder with a prevalence of about one in 500 live-born males. KS is associated with hypogonadism and is suspected to cause variable physical and cognitive abnormalities. As a supernumerary X chromosome is also associated with infertility, sound animal models for KS are difficult to obtain.

Methods: Male mice with two X chromosomes (XX*Y) were derived from fathers carrying a structurally rearranged Y chromosome (Y*) that resulted in close attachment of a part of the Y chromosome to one X. These animals seem to mimic physiological features of the human KS. The aim of this study was a behavioral characterization of this mouse model. 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.

Results and discussion: All mice appeared healthy. XX*Y mice did not differ from their wildtype littermates with respect to locomotion, exploration and anxiety related behavior. XX*Y male mice, however exhibited no significant learning performance in contrast to wildtype XY* males which readily learned the task. These findings support the idea that the presence of a supernumerary X in male mice influences cognitive abilities and that the 41, XX*Y mouse model can also be utilized to study X chromosomal imbalance and cognition experimentally.

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