Abstract
The impact of two mouse models is reviewed, the Four Core Genotypes and XY* models. The models are useful for determining if the causes of sex differences in phenotypes are either hormonal or sex chromosomal, or both. Used together, the models also can distinguish between the effects of X or Y chromosome genes that contribute to sex differences in phenotypes. To date, the models have been used to uncover sex chromosome contributions to sex differences in a wide variety of phenotypes, including brain and behavior, autoimmunity and immunity, cardiovascular disease, metabolism, and Alzheimer's Disease. In some cases, use of the models has been a strategy leading to discovery of specific X or Y genes that protect from or exacerbate disease. Sex chromosome and hormonal factors interact, in some cases to reduce the effects of each other. Future progress will come from more extensive application of these models, and development of similar models in other species.