We use several mouse models to measure the effects of sex chromosomes on physiology and disease.
The Four Core Genotypes model compares XX and XY mice that have the same kind of gonads. The model is explained in this introductory video, and in several review articles: PMIDs 21613996, 19028515, 23361913, 24509348, 27999654. Four genotypes are produced, XX and XY mice with testes, and XX and XY mice with ovaries. When hormone levels are kept as similar as possible between groups, these comparisons show when a sex difference is caused by the inherent XX vs. XY difference in expression of X and Y genes within cells.
The XY* model compares mice with different numbers of X or Y chromosomes. Four genotypes are very similar to XO, XX, XY, and XXY. The Y chromosome carries Sry, the testis-determining gene, so that genotypes with the Y chromosome are gonadal males. This model is discussed in an introductory video, “An experimental approach to identify X and Y genes that are primary causes of sex differences in non-gonadal traits”, and in several articles: PMIDs 27870435, 27999654, 26833834. Two comparisons show the effect of having one vs. two X chromosomes: XO vs. XX, or XY vs. XXY. Two comparisons show the effect of having a Y chromosome or not: XO vs. XY, XX vs. XXY.
The Sex Chromosome Trisomy model compares mice that are XX, XY, XXY, and XYY, with each genotype occurring within litters as gonadal males or females. The model allows testing the effects of sex chromosome trisomy (XXY, XYY) on physiology and disease. This model is discussed in these articles: PMIDs 23926958, 24923877.