Four-Core Genotypes mice harbour a 3.2MB X-Y translocation that perturbs Tlr7 dosage

Panten, Jasper; Prete, Stefania Del; Cleland, James P.; Saunders, Lauren M.; van Riet, Job; Schneider, Anja; Ginno, Paul; Schneider, Nina; Koch, Marie-Luise; Gerstung, Moritz; Stegle, Oliver; Turner, James M. A.; Heard, Edith; Odom, Duncan T.

doi:10.1101/2023.12.04.569933

Cited by 2 publications

References 36 publications

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Sex chromosomes and hormones independently influence healthy brain development but act similarly after cranial radiation

Yeung,

DeYoung,

Spring

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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The course of normal development and response to pathology are strongly influenced by biological sex. For instance, female childhood cancer survivors who have undergone cranial radiation therapy (CRT) tend to display more pronounced cognitive deficits than their male counterparts. Sex effects can be the result of sex chromosome complement (XX vs. XY) and/or gonadal hormone influence. The contributions of each can be separated using the four-core genotype mouse model (FCG), where sex chromosome complement and gonadal sex are decoupled. While studies of FCG mice have evaluated brain differences in adulthood, it is still unclear how sex chromosome and sex hormone effects emerge through development in both healthy and pathological contexts. Our study utilizes longitudinal MRI with the FCG model to investigate sex effects in healthy development and after CRT in wildtype and immune-modified Ccl2 -knockout mice. Our findings in normally developing mice reveal a relatively prominent chromosome effect prepubertally, compared to sex hormone effects which largely emerge later. Spatially, sex chromosome and hormone influences were independent of one another. After CRT in Ccl2 -knockout mice, both male chromosomes and male hormones similarly improved brain outcomes but did so more separately than in combination. Our findings highlight the crucial role of sex chromosomes in early development and identify roles for sex chromosomes and hormones after CRT-induced inflammation, highlighting the influences of biological sex in both normal brain development and pathology.

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Sex chromosomes and hormones independently influence healthy brain development but act similarly after cranial radiation

Yeung,

DeYoung,

Spring

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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A second X chromosome improves cognition in aging male and female mice

Marino,

Wang,

Merrihew

et al. 2024

Preprint

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Women show resilience to cognitive aging, in the absence of dementia, in many populations. To dissect sex differences, we utilized the FCG and XY* mouse models. Female gonads and sex chromosomes improved cognition in aging mice of both sexes. Further, presence of a second X in male and female mice conferred cognitive resilience while its absence in females blocked it. In the hippocampal proteome of aging female mice, the second X increased proteins involved in synaptogenesis signaling - a potential pathway to improved cognition.

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Four-Core Genotypes mice harbour a 3.2MB X-Y translocation that perturbs Tlr7 dosage

Cited by 2 publications

References 36 publications

Sex chromosomes and hormones independently influence healthy brain development but act similarly after cranial radiation

Sex chromosomes and hormones independently influence healthy brain development but act similarly after cranial radiation

A second X chromosome improves cognition in aging male and female mice

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