Although aberrant karyotypes which cause similar phenotypes have been reported in other mammalian species, none of these animals can adequately serve as an experimental model, primarily due to simple practical concerns.Consequently, it was a breakthrough when a mouse line with a mutated Y chromosome was discovered (Eicher ., 1991) and after the application of a staggered breeding scheme (Fig.The possession of a single, active X chromosome can therefore be seen as a prerequisite for the correct formation of a male phenotype and is as important as the presence of a Y chromosome.
In mammals, X chromosome inactivation (XCI) controls the genetic imbalance arising from the X: autosome ratio, i.e.
the different number of X chromosomes between the sexes.
Meiotic non-disjunction of chromosomes can occur during the differentiation of gametes and results in aberrant karyotypes leading to various diseases, as long as the extra chromosomes are not causing lethal alterations.
Among such disorders, Klinefelter's syndrome, which severely affects the male phenotype, is the most frequent (Lanfranco ., 2006; Wikström and Dunkel, 2008).
., 1991; Hunt and Eicher 1991).(A) Animals were obtained from the B6Ei. The spontaneously mutated male mice carried a Y chromosome, designated Y*, which acquired a new centromere distally and lost the normal centromere.
(B) Breeding such phenotypically normal and fertile 40, XY* males to 40, XX females provoked sex chromosomal non-disjunction events during meiosis and result in ∼25% of the male offspring exhibiting the 41, XX* karyotype.1) resulted in the generation of male mice with a supernumerary X chromosome which showed a phenotype comparable to Klinefelter's syndrome.To date, from the initial strain, two mouse models, the 41, XXY (Lue ., 2009), have been established and characterized.In addition, the male phenotype depends on the presence of a single X chromosome which needs to be always active.The situation in females is different; two X chromosomes are present and their expression activity has to be balanced.These males have been demonstrated to resemble many features of Klinefelter's syndrome, although the Y chromosome is not completely separated but in close association with one of the X chromosomes (Lewejohann ., 1991; Hunt and Eicher 1991).(A) Animals were obtained from the B6Ei. The spontaneously mutated male mice carried a Y chromosome, designated Y*, which acquired a new centromere distally and lost the normal centromere.