Mouse model systems to study sex chromosome genes and behavior: Relevance to humans

Cox, Kimberly; Bonthuis, Paul J.; Rissman, Emilie F.

doi:10.1016/j.yfrne.2013.12.004

Cited by 61 publications

(60 citation statements)

References 159 publications

(201 reference statements)

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“…In that study, XX females were less social than XY females and XX males, but did not differ statistically from XY males in any behavioral measure. Because the FCG cross produces mice of both gonadal sexes with either XX or XY genotypes, it is not possible to assess whether sex chromosome effects are caused by the presence of 2 X-chromosomes, or the absence of a Y-chromosome (reviewed in (Cox et al, 2014). Moreover, in addition to the sex chromosome differences, while both the FCG and Y* mouse models are backcrossed into the B6 background strain, there are other genetic differences between the two strains (Eicher et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, in addition to the sex chromosome differences, while both the FCG and Y* mouse models are backcrossed into the B6 background strain, there are other genetic differences between the two strains (Eicher et al, 1991). One obvious source of behavioral differences is that the two strains have Y-chromosomes from different origins (reviewed in (Cox et al, 2014)). This difference has been shown to affect offspring behavior (Maxson et al, 1979; Nelson et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…Mating these males with wild-type females produces offspring of both sexes with either 1 or 2 copies of X-chromosomes (Table 1) (Eicher et al, 1991; Burgoyne et al, 1998; Cox et al, 2014). Our Y* colony was established with XY* males (in the 6JEiJ substrain) and C57BL/6J (B6) females purchased from The Jackson Laboratory (Bar Harbor, ME; stock numbers 002021 and 000924), and maintained in the B6 sub-strain.…”

Section: Methodsmentioning

confidence: 99%

“…In addition, sex chromosome complement correlates with differences in the brain and behavior in mice (reviewed in Cox et al, 2014). The basic mechanisms that cause sex differences are important to study and, more broadly, can also help us understand neurobehavioral diseases, many of which are sexually dimorphic in their incidence, severity, and/or timing of onset.…”

Section: Introductionmentioning

confidence: 99%

“…These mice (Eicher et al, 1991; Burgoyne et al, 1998; Cox et al, 2014) produce offspring with four sex chromosome genotypes: XY males, XXY males, XO females, and XX females (hereafter referred to as 1X males, 2X males, 1X females, and 2X females; Table 1). In order to control for the hormonal differences seen in adult mice, prepubertal mice were tested for social and anxiety behavior.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Number of X-chromosome genes influences social behavior and vasopressin gene expression in mice

Cox

Quinnies

Eschendroeder

et al. 2015

Psychoneuroendocrinology

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Summary Sex differences in behavior are widespread and often caused by hormonal differences between the sexes. In addition to hormones, the composition and numbers of the sex chromosomes also affect a variety of sex differences. In humans, X-chromosome genes are implicated in neurobehavioral disorders (i.e. fragile-X, autism). To investigate the role of X-chromosome genes in social behavior, we used a mouse model that has atypical sex chromosome configurations resembling Turner (45, XO) and Klinefelter syndromes (47, XXY). We examined a number of behaviors in juvenile mice. Mice with only one copy of most X-chromosome genes, regardless of gonadal sex, were less social in dyadic interaction and social preference tasks. In the elevated plus maze, mice with one X-chromosome spent less time in the distal ends of the open arms as compared to mice with two copies of X-chromosome genes. Using qRTPCR, we noted that amygdala from female mice with one X-chromosome had higher expression levels of vasopressin (Avp) as compared to mice in the other groups. Finally, in plasma from girls with Turner syndrome we detected reduced vasopressin (AVP) concentrations as compared to control patients. These novel findings link sex chromosome genes with social behavior via concentrations of AVP in brain, adding to our understanding of sex differences in neurobehavioral disorders.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Number of X-chromosome genes influences social behavior and vasopressin gene expression in mice

Cox

Quinnies

Eschendroeder

et al. 2015

Psychoneuroendocrinology

Self Cite

View full text Add to dashboard Cite

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The mouse as a model of fundamental concepts related to Turner syndrome

Arnold

2019

American J of Med Genetics Pt C

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Although XO mice do not show many of the overt phenotypic features of Turner syndrome (TS; 45,X or XO), mice and humans share different classes of genes on the X chromosome that are more or less likely to cause TS phenotypes. Based on the evolutionary history of the sex chromosomes, and the pattern of dosage balancing among sex chromosomal and autosomal genes in functional gene networks, it is possible to prioritize types of X genes for study as potential causes of features of TS. For example, X‐Y gene pairs are among the most interesting because of the convergent effects of X and Y genes that both are likely to prevent the effects of TS in XX and XY individuals. Many of the high‐priority genes are shared by mouse and human X chromosomes, but are easier to study in genetically tractable mouse models. Several mouse models, used primarily for the study of sex differences in physiology and disease, also produce XO mice that can be investigated to understand the effects of X monosomy. Using these models will lead to the identification of specific X genes that make a difference when present in one or two copies. These studies will help to achieve a better appreciation of the contribution of these specific X genes to the syndromic features of TS.

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Hormone profiles of the African pygmy mouse Mus minutoides, a species with XY female sex reversal

Veyrunes,

Perez,

Heitzmann

et al. 2023

J Exp Zool Pt A

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In mammals, most sex differences in phenotype are controlled by gonadal hormones, but recent work on transgenic mice has shown that sex chromosomes can have a direct influence on sex‐specific behaviors. In this study, we take advantage of the naturally occurring sex reversal in a mouse species, Mus minutoides, to investigate for the first time the relationship between sex chromosomes, hormones, and behaviors in a wild species. In this model, a feminizing variant of the X chromosome, named X*, produces three types of females with different sex chromosome complements (XX, XX*, and X*Y), associated with alternative behavioral phenotypes, while all males are XY. We thus compared the levels of three major circulating steroid hormones (testosterone, corticosterone, and estradiol) in the four sex genotypes to disentangle the influence of sex chromosomes and sex hormones on behavior. First, we did not find any difference in testosterone levels in the three female genotypes, although X*Y females are notoriously more aggressive. Second, in agreement with their lower anxiety‐related behaviors, X*Y females and XY males display lower baseline corticosterone concentration than XX and XX* females. Instead of a direct hormonal influence, this result rather suggests that sex chromosomes may have an impact on the baseline corticosterone level, which in turn may influence behaviors. Third, estradiol concentrations do not explain the enhanced reproductive performance and maternal care behavior of the X*Y females compared to the XX and XX* females. Overall, this study highlights that most of the behaviors varying along with sex chromosome complement of this species are more likely driven by genetic factors rather than steroid hormone concentrations.

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Mouse model systems to study sex chromosome genes and behavior: Relevance to humans

Cited by 61 publications

References 159 publications

Number of X-chromosome genes influences social behavior and vasopressin gene expression in mice

Number of X-chromosome genes influences social behavior and vasopressin gene expression in mice

The mouse as a model of fundamental concepts related to Turner syndrome

Hormone profiles of the African pygmy mouse Mus minutoides, a species with XY female sex reversal

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