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Animal models for Klinefelter s syndrome and their relevance for the clinic Wistuba JMol Hum Reprod 2010[Jun]; 16 (6): 375-85In mammals, the contribution of the Y chromosome is paramount for male sexual determination; however, the presence of a single functional X chromosome is also of importance. In contrast to females where X inactivation is seen; the X chromosome of the male stays active. When, due to meiotic non-disjunction events, males are born with a supernumerary X chromosome, the resulting 47, XXY karyotype is referred to as Klinefelter's syndrome. This frequent genetic condition is most commonly associated with infertility, hypogonadism, gynecomastia and cognitive impairments. The condition has also been associated with a reduced life expectancy, insulin resistance, dyslipidemia, increased body fat mass and reduced bone mineral content. In a variety of species, male animals with karyotypes resembling Klinefelter's syndrome arise and develop a subset of features similar to those seen in humans. The availability of these animals is driving efforts to experimentally address the pathophysiology of the condition. To date, two models, 41, XXY and 41, XX(Y)* (mutated Y chromosome) male mice, have been established which resemble aspects of the pathophysiology of Klinefelter's syndrome. Experiments performed in these models confirm that the presence of a supernumerary X chromosome causes germ cell loss, cognitive deficits, Leydig cell hyperplasia, and that their Sertoli cells are capable of supporting germ cells of normal karyotype. This review summarizes the generation and characterization of the animal models for Klinefelter's syndrome and suggests experimental strategies to improve our understanding of the mechanisms underlying the pathophysiology of Klinefelter's syndrome.|*Disease Models, Animal[MESH]|Animals[MESH]|Biomedical Research/methods/trends[MESH]|Chromosome Aberrations[MESH]|Chromosomes, Human, X/genetics[MESH]|Female[MESH]|Humans[MESH]|Klinefelter Syndrome/genetics/*pathology/*therapy[MESH]|Male[MESH]|Mammals/genetics[MESH]|Mice[MESH]|Models, Biological[MESH] |
