XXY 和 XYY 性染色体三体小鼠模型：代谢和运动表现。
The Sex Chromosome Trisomy mouse model of XXY and XYY: metabolism and motor performance.
机构信息
Department of Integrative Biology & Physiology, University of California, Los Angeles, 405 Hilgard Avenue, Los Angeles, CA 90095, USA.
Laboratory of Neuroendocrinology of the Brain Research Institute, University of California, Los Angeles, 405 Hilgard Avenue, Los Angeles, CA 90095, USA.
出版信息
Biol Sex Differ. 2013 Aug 8;4(1):15. doi: 10.1186/2042-6410-4-15.
BACKGROUND
Klinefelter 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.
METHODS
In 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.
RESULTS
Before 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.
CONCLUSIONS
We 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.
背景
克氏综合征（KS）由 XXY 染色体核型引起，其特征是睾酮水平低、不育、认知缺陷，以及肥胖和糖尿病等健康问题的患病率增加。由于低睾酮水平与性染色体组成混杂在一起，因此在人类研究或 KS 的小鼠模型中，很难将直接的遗传效应与激素效应分开。
方法
在这项研究中，我们提出了性染色体三体（SCT）小鼠模型，该模型在同一窝中产生 XXY、XYY、XY 和 XX 小鼠，每种基因型都具有睾丸或卵巢。性染色体组成和性腺类型的独立性允许更好地识别不依赖于性腺激素水平的性染色体效应。所有小鼠均进行性腺切除术并接受睾酮治疗 3 周。测量体重、身体成分和运动功能。
结果
在激素处理之前，XXY 雌雄小鼠的体重和相对脂肪质量均明显大于 XY 小鼠。去势和睾酮替代后，XXY 小鼠（雌雄）的体重和相对脂肪质量仍明显大于 XY 小鼠，但相对瘦体重较少。XXY 小鼠的肝脏、性腺脂肪垫和腹股沟脂肪垫重量也较高，与性腺性别无关。在这些指标中的几个指标中，XX 小鼠也与 XY 小鼠不同，并且性腺雄性和雌性在几乎所有代谢指标上都存在显著差异。在去势和睾酮治疗前后的性腺雌性小鼠中也观察到性染色体效应（除睾丸大小外），表明它们不反映睾丸分泌物水平的组间差异。XYY 小鼠的体重和代谢变量与 XY 小鼠相似，但在运动任务方面的表现不如其他组。
结论
我们发现，用于 XXY 和 XYY 的新型 SCT 小鼠模型再现了这些非整倍体患者中发现的特征。我们表明，与这些综合征中的激素效应相比，该模型具有揭示遗传效应的巨大潜力，因为许多表型在从未暴露于睾丸分泌物的 XXY 与 XY 性腺雌性小鼠中有所不同。
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