The Sex Chromosome Trisomy mouse model of XXY and XYY: metabolism and motor performance
| Autor: | Tuck Ngun, Negar Ghahramani, Eric Vilain, Hayk Barseghyan, Xuqi Chen, Arthur P. Arnold, Karen Reue, Rebecca McClusky, Shayna M. Williams-Burris |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
medicine.medical_specialty
Mouse Biology Y chromosome Fat pad X chromosome Gender Studies 03 medical and health sciences 0302 clinical medicine Endocrinology XXY Internal medicine medicine Obesity Sex chromosome trisomy Testosterone 030304 developmental biology Klinefelter 0303 health sciences Research Karyotype XYY Body weight medicine.disease Lean body mass Klinefelter syndrome 030217 neurology & neurosurgery Hormone |
| Zdroj: | Biology of Sex Differences Chen, Xuqi; Williams-Burris, Shayna M; McClusky, Rebecca; Ngun, Tuck C; Ghahramani, Negar; Barseghyan, Hayk; et al.(2013). The Sex Chromosome Trisomy mouse model of XXY and XYY: metabolism and motor performance. Biology of Sex Differences, 4(1), 15. doi: http://dx.doi.org/10.1186/2042-6410-4-15. Retrieved from: http://www.escholarship.org/uc/item/5jc531qb |
| ISSN: | 2042-6410 |
| DOI: | 10.1186/2042-6410-4-15 |
| Popis: | BackgroundKlinefelter syndrome (KS), caused by XXY karyotype, is characterized by low testosterone, infertility, cognitive deficits, and increased prevalence of health problems including obesity and diabetes. It has been difficult to separate direct genetic effects from hormonal effects in human studies or in mouse models of KS because low testosterone levels are confounded with sex chromosome complement.MethodsIn this study, we present the Sex Chromosome Trisomy (SCT) mouse model that produces XXY, XYY, XY, and XX mice in the same litters, each genotype with either testes or ovaries. The independence of sex chromosome complement and gonadal type allows for improved recognition of sex chromosome effects that are not dependent on levels of gonadal hormones. All mice were gonadectomized and treated with testosterone for 3 weeks. Body weight, body composition, and motor function were measured.ResultsBefore hormonal manipulation, XXY mice of both sexes had significantly greater body weight and relative fat mass compared to XY mice. After gonadectomy and testosterone replacement, XXY mice (both sexes) still had significantly greater body weight and relative fat mass, but less relative lean mass compared to XY mice. Liver, gonadal fat pad, and inguinal fat pad weights were also higher in XXY mice, independent of gonadal sex. In several of these measures, XX mice also differed from XY mice, and gonadal males and females differed significantly on almost every metabolic measure. The sex chromosome effects (except for testis size) were also seen in gonadally female mice before and after ovariectomy and testosterone treatment, indicating that they do not reflect group differences in levels of testicular secretions. XYY mice were similar to XY mice on body weight and metabolic variables but performed worse on motor tasks compared to other groups.ConclusionsWe find that the new SCT mouse model for XXY and XYY recapitulates features found in humans with these aneuploidies. We illustrate that this model has significant promise for unveiling the role of genetic effects compared to hormonal effects in these syndromes, because many phenotypes are different in XXY vs. XY gonadal female mice which have never been exposed to testicular secretions. |
| Databáze: | OpenAIRE |
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