XXY male mice: An experimental model for Klinefelter syndrome

Klinefelter syndrome (47,XXY) is the most common sex chromosome aneuploidy in men. Thus, it is important to establish an experimental animal model to explore its underlying molecular mechanisms. Mice with a 41,XXY karyotype w ere produced by mating wild-type male mice with chimeric female mice carryi ng male embryonic stem cells. The objectives of the present study were to c haracterize the testicular phenotype of adult XXY mice and to examine the o ntogeny of loss of germ cells in juvenile XXY mice. In the first experiment the testicular phenotypes of four adult XXY mice and four littermate contr ols (40,XY) were studied. XXY mice were identified by either Southern hybri dization or karyotyping and were further confirmed by fluorescence in situ hybridization. The results showed that the testis weights of adult XXY mice (0.02 +/- 0.01 g) were dramatically decreased compared with those of the c ontrols (0.11 +/- 0.01 g). Although no significant differences were apparen t in plasma testosterone levels, the mean plasma LH and FSH levels were ele vated in adult XXY mice compared with controls. The testicular histology of adult XXY mice showed small seminiferous tubules with varying degrees of i ntraepithelial vacuolization and a complete absence of germ cells. Hypertro phy and hyperplasia of Leydig cells were observed in the interstitium. Elec tron microscopic examination showed Sertoli cells containing scanty amounts of cytoplasm and irregular nuclei with prominent nucleoli. The junctional region between Sertoli cells appeared normal. In some tubules, nests of app arently degenerating Sertoli cells were found. In the second experiment the ontogeny of germ cell loss in juvenile XXY mice and their littermate contr ols was studied. Spermatogonia were found and appeared to be morphologicall y normal in juvenile XXY mice. Progressive loss of germ cells occurred with in 10 days after birth. This resulted in the absence of germ cells in the a dult XXY mice. We conclude that a progressive loss of germ cells occurring in early postnatal life results in the complete absence of germ cells in ad ult XXY mice. The XXY mouse provides an experimental model for its human XX Y counterpart, Klinefelter syndrome.