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Publication : Sexual differentiation in the developing mouse brain: contributions of sex chromosome genes.

First Author  Wolstenholme JT Year  2013
Journal  Genes Brain Behav Volume  12
Issue  2 Pages  166-80
PubMed ID  23210685 Mgi Jnum  J:206774
Mgi Id  MGI:5551962 Doi  10.1111/gbb.12010
Citation  Wolstenholme JT, et al. (2013) Sexual differentiation in the developing mouse brain: contributions of sex chromosome genes. Genes Brain Behav 12(2):166-80
abstractText  Neural sexual differentiation begins during embryogenesis and continues after birth for a variable amount of time depending on the species and brain region. Because gonadal hormones were the first factors identified in neural sexual differentiation, their role in this process has eclipsed investigation of other factors. Here, we use a mouse with a spontaneous translocation that produces four different unique sets of sex chromosomes. Each genotype has one normal X-chromosome and a unique second sex chromosome creating the following genotypes: XY(*x) , XX, XY(*) , XX(Y) (*) . This Y(*) mouse line is used by several laboratories to study two human aneuploid conditions: Turner and Klinefelter syndromes. As sex chromosome number affects behavior and brain morphology, we surveyed brain gene expression at embryonic days 11.5 and 18.5 to isolate X-chromosome dose effects in the developing brain as possible mechanistic changes underlying the phenotypes. We compared gene expression differences between gonadal males and females as well as individuals with one vs. two X-chromosomes. We present data showing, in addition to genes reported to escape X-inactivation, a number of autosomal genes are differentially expressed between the sexes and in mice with different numbers of X-chromosomes. Based on our results, we can now identify the genes present in the region around the chromosomal break point that produces the Y(*) model. Our results also indicate an interaction between gonadal development and sex chromosome number that could further elucidate the role of sex chromosome genes and hormones in the sexual differentiation of behavior.
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