What does the "four core genotypes" mouse model tell us about sex differences in the brain and other tissues?
The "four core genotypes" (FCG) model comprises mice in which sex chromosome complement (XX vs. XY) is unrelated to the animal's gonadal sex. The four genotypes are XX gonadal males or females, and XY gonadal males or females. The model allows one to measure (1) the differences in phenotypes caused by sex chromosome complement (XX vs. XY), (2) the differential effects of ovarian and testicular secretions, and (3) the interactive effects of (1) and (2). Thus, the FCG model provides new information regarding the origins of sex differences in phenotype that has not been available from studies that manipulate gonadal hormone levels in normal XY males and XX females. Studies of the FCG model have uncovered XX vs. XY differences in behaviors (aggression, parenting, habit formation, nociception, social interactions), gene expression (septal vasopressin), and susceptibility to disease (neural tube closure and autoimmune disease) not mediated by gonadal hormones. Some sex chromosome effects are mediated by sex differences in dose of X genes or their parental imprint. Future studies will identify the genes involved and their mechanisms of action.
Arnold
Arthur P
AP
Department of Physiological Science, Laboratory of Neuroendocrinology of the Brain Research Institute, University of California, Los Angeles, CA 90095-1606, USA. arnold@ucla.edu
Chen
Xuqi
X
D000374:Aggression / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000502:physiology; D012734:Disorders of Sex Development; D005260:Female; D005838:Genotype; D008297:Male; D051379:Mice; D023421:Models, Animal; D009436:Neural Tube Defects / Q000235:genetics; D016487:Parenting; D012727:Sex Characteristics; D012729:Sex Chromosome Aberrations; D012730:Sex Chromosomes / Q000235:genetics*; D019849:Sex Determination Processes; D051876:Sex-Determining Region Y Protein / Q000235:genetics; D012919:Social Behavior; D014960:X Chromosome / Q000235:genetics; D014998:Y Chromosome / Q000235:genetics
D051876:Sex-Determining Region Y Protein; C497746:Sry protein, mouse