UCLA

The Four Core Genotypes (FCG) transgenic mouse model allows us to investigate if an observed sex difference in phenotype is caused by gonadal hormones, sex chromosome effects, or both1. The FCG model currently exists in mice only, limiting generalizability across species. Not only does developing an FCG model in rats improve the applicability of the results, but rats have advantages as a model organism when studying neurodevelopmental, cardiovascular, and substance use disorders due to their larger size and docile nature. To make rats like FCG mice, the region of the Y chromosome harboring Sry, the testis-determining gene was mutated (producing the YΔ chromosome), reducing the number of Sry genes and preventing testis development. In addition, a bacterial artificial chromosome (BAC) encoding Sry was inserted as a transgene in an autosome in several transgenic rat lines, producing XX rats with testes. One goal of the present study was to locate the insertion point of the Sry transgene. Using a commercially available Y Chromosome paint, and a fluorescently labeled Sry transgene probe, we performed metaphase fluorescent in-situ hybridization (FISH), to locate the transgene inserted in Chromosome 11 in transgenic line 208, Chromosome 20 in line 424, and Chromosome 2 in line 733. We also compared estrous cycling of gonadal females with different sex chromosome complements, as a bioassay for complex endocrine regulatory mechanisms regulating ovulation and estrus. We compared XX or XXYΔ sex chromosomes, by observing the type and concentration of cells collected in daily vaginal swabs of both groups. This experiment revealed no difference in estrous cycle length between gonadal females with or without a YΔ chromosome, therefore uncovering no effect of sex chromosome complement on factors controlling estrus.