2016
DOI: 10.18632/aging.100997
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Abstract: Stroke is a sexually dimorphic disease. Elderly women not only have higher stroke incidence than age-matched men, but also have poorer recovery and higher morbidity and mortality after stroke. In older, post-menopausal women, gonadal hormone levels are similar to that of men. This suggests that tissue damage and functional outcomes are influenced by biologic sex (XX vs. XY) rather than the hormonal milieu at older ages. We employed the Four Core Genotype (FCG) mouse model to study the contribution of sex chrom… Show more

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Cited by 76 publications
(52 citation statements)
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References 47 publications
(52 reference statements)
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“…In mouse, the sex chromosome content and presence/absence of male-determining Sry gene have been elegantly manipulated in gonad-intact and gonad-ablated animals. These experiments have revealed effects of gonadal hormones versus other sex chromosome effects, for phenotypes including growth, metabolism, and stroke sensitivity with age [1, 83] . In the future, it will be of interest to use these powerful mouse models to further investigate sex-specific regulation of aging and life span.…”
Section: Discussionmentioning
confidence: 99%
“…In mouse, the sex chromosome content and presence/absence of male-determining Sry gene have been elegantly manipulated in gonad-intact and gonad-ablated animals. These experiments have revealed effects of gonadal hormones versus other sex chromosome effects, for phenotypes including growth, metabolism, and stroke sensitivity with age [1, 83] . In the future, it will be of interest to use these powerful mouse models to further investigate sex-specific regulation of aging and life span.…”
Section: Discussionmentioning
confidence: 99%
“…When a similar study was conducted on aging mice, however, the opposite result was obtained. In that case, group differences in type of gonad had little effect, but XX mice had larger infarcts than XY mice (McCullough et al, 2016). In aging mice, the group differences were not attributable to levels of gonadal hormones.…”
Section: Applying the Theory To Whole Animal Physiologymentioning
confidence: 94%
“…FCG mouse are created by mating a WT female (XXF) and a transgenic male (XYM) in which the testis determining gene, Sry has been deleted from the Y chromosome and is inserted onto an autosome (Arnold et al 2016; Li et al 2014). The resulting four mouse lines are XXF (WT), XXM (with the Sry inherited on an autosome so the resulting animals develop testis and are phenotypically male despite the XX chromosome compliment), XYF (that have the Y chromosome but no Sry and thus develop ovaries and secrete estrogen), and XYM (with Sry inherited on an autosome) (McCullough et al 2016). Early works suggest that the contribution of chromosomal compliment differs in the aged brain compared to that seen in young.…”
Section: Sex-specific Genetic and Epigenetic Influences And Immune Rementioning
confidence: 99%
“…Early works suggest that the contribution of chromosomal compliment differs in the aged brain compared to that seen in young. Using the FCG mouse model, Liu et al showed that in terms of infarct size, neurologic deficit score and immune cells infiltration and activation, the aged animals with XX chromosomes had worse stroke outcomes when compared to animals with XY chromosome (McCullough et al 2016). In the same model, when we studied young gonadally intact and gonadectimized mice, we found that in the young brain, the infarct size is predominantly driven by gonadal sex (ovaries versus testis) rather than chromosomal sex (Manwani et al 2015).…”
Section: Sex-specific Genetic and Epigenetic Influences And Immune Rementioning
confidence: 99%