Dataset Information

The Sex Chromosome Trisomy mouse model of XXY and XYY: metabolism and motor performance.

ABSTRACT:

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.

SUBMITTER: Chen X

PROVIDER: S-EPMC3751353 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Publications

The Sex Chromosome Trisomy mouse model of XXY and XYY: metabolism and motor performance.

Chen Xuqi X Williams-Burris Shayna M SM McClusky Rebecca R Ngun Tuck C TC Ghahramani Negar N Barseghyan Hayk H Reue Karen K Vilain Eric E Arnold Arthur P AP

Biology of sex differences 20130808 1

<h4>Background</h4>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.<h4>Methods</h4>In this study, we present the Sex Chromosome Trisomy (SCT) mouse mo ...[more]

PMID: 23926958

Similar Datasets

Project description:BackgroundSex Chromosome Trisomies (SCTs; XXX, XXY, XYY) are genetic conditions that are associated with increased risk for neurodevelopmental problems and psychopathology. There is a great need for early preventive intervention programs to optimize outcome, especially considering the increase in prenatal diagnoses due to recent advances in non-invasive prenatal screening. This study is the first to evaluate efficacy of a neurocognitive training in children with SCT. As social behavioral problems have been identified as among the key areas of vulnerability, it was targeted at improving a core aspect of social cognition, the understanding of social cues from facial expressions.MethodsParticipants were 24 children with SCT and 18 typically developing children, aged 4-8 years old. Children with SCT were assigned to a training (n = 13) or waiting list (no-training) group (n = 11). Children in the training group completed a neurocognitive training program (The Transporters), aimed to increase understanding of facial emotions. Participants were tested before and after the training on facial emotion recognition and Theory of Mind abilities (NEPSY-II), and on social orienting (eyetracking paradigm). The SCT no-training group and typically developing control group were also assessed twice with the same time interval without any training. Feasibility of the training was evaluated with the Social Validity Questionnaire filled out by the parents and by children's ratings on a Visual Analog Scale.ResultsThe SCT training group improved significantly more than the SCT no-training and TD no-training group on facial emotion recognition (large effect size; ηp2 = 0.28), performing comparable to typical controls after completing the training program. There were no training effects on ToM abilities and social orienting. Both children and parents expressed satisfaction with the feasibility of the training.ConclusionsThe significant improvement in facial emotion recognition, with large effect sizes, suggests that there are opportunities for positively supporting the development of social cognition in children with an extra X- or Y-chromosome, already at a very young age. This evidence based support is of great importance given the need for preventive and early training programs in children with SCT, aimed to minimize neurodevelopmental impact.

Dataset Information

The Sex Chromosome Trisomy mouse model of XXY and XYY: metabolism and motor performance.

Background

Methods

Results

Conclusions

Publications

The Sex Chromosome Trisomy mouse model of XXY and XYY: metabolism and motor performance.

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