In the human, sex chromosome aneuploidy is associated with specific phenotypic abnormalities and with decreased fertility or infertility. The somatic abnormalities are hypothesized to be the result of altered levels of sex chromosome gene expression, and the germ cell abnormalities to reflect either altered gene expression, disruption of sex chromosome pairin during meiosis, or both. However, for technical and ethical reasons there are virtually no data on the nature or the timing of the germ cell abnormalities. Furthermore, the relative scarcity of sex chromosome aneuploidy in experimental animals such as the mouse has limited investigations in other species as well. Using a recently described murine Y chromosome rearrangement, Y*, it has become possible to breed for specifi categories of sex chromosome aneuploidy, and thereby to evaluate the phenotypic effect of sex chromosome abnormalities, including effects on ger cell viability and function. In the proposed research we intend to utilize the different abnormalities to analyze the effect of abnormal X chromosome dosage in both the male and female mouse and, in the male, to separate the effect on meiosis of abnormal sex chromosome dosage from abnormalities arising due to disruption of the normal sex chromosome pairing process. Specifically, the three major objectives of the proposed research are: 1) To assess the role of sex chromosome pairing on germ cells in male and female meiosis. 2) To characterize growth, development and germ cell behavior in the XXY mouse and to assess the appropriateness of these mice as a model for the human Klinefelter Syndrome. 3) To investigate the possibility that the parental origin of the single X chromosome influences the survival and/or fertility of XO individuals.
| Hunt, P A; Worthman, C; Levinson, H et al. (1998) Germ cell loss in the XXY male mouse: altered X-chromosome dosage affects prenatal development. Mol Reprod Dev 49:101-11 |
| Hunt, P A; LeMaire, R (1992) Sex-chromosome pairing: evidence that the behavior of the pseudoautosomal region differs during male and female meiosis. Am J Hum Genet 50:1162-70 |
| Handel, M A; Hunt, P A (1992) Sex-chromosome pairing and activity during mammalian meiosis. Bioessays 14:817-22 |
| Hunt, P A (1991) Survival of XO mouse fetuses: effect of parental origin of the X chromosome or uterine environment? Development 111:1137-41 |
| Handel, M A; Hunt, P A (1991) Genomic imprinting: male mice with uniparentally derived sex chromosomes. Mol Reprod Dev 28:337-40 |
| Handel, M A; Hunt, P A; Kot, M C et al. (1991) Role of sex chromosomes in the control of male germ-cell differentiation. Ann N Y Acad Sci 637:64-73 |
