caa a22 4500 606201505 CHVBK 20210128100948.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s00429-014-0875-9 doi (NATIONALLICENCE)springer-10.1007/s00429-014-0875-9 Triangulating the sexually dimorphic brain through high-resolution neuroimaging of murine sex chromosome aneuploidies [Elektronische Daten] [Armin Raznahan, YanHe Lue, Frank Probst, Deanna Greenstein, Jay Giedd, Christina Wang, Jason Lerch, Ronald Swerdloff] Murine sex chromosome aneuploidies (SCAs) provide powerful models for charting sex chromosome influences on mammalian brain development. Here, building on prior work in X-monosomic (XO) mice, we use spatially non-biased high-resolution imaging to compare and contrast neuroanatomical alterations in XXY and XO mice relative to their wild-type XX and XY littermates. First, we show that carriage of a supernumerary X chromosome in XXY males (1) does not prevent normative volumetric masculinization of the bed nucleus of the stria terminalis (BNST) and medial amygdala, but (2) causes distributed anatomical alterations relative to XY males, which show a statistically unexpected tendency to be co-localized with and reciprocal to XO-XX differences in anatomy. These overlaps identify the lateral septum, BNST, ventral group thalamic nuclei and periaqueductal gray matter as regions with replicable sensitivity to X chromosome dose across two SCAs. We then harness anatomical variation across all four karyotype groups in our study—XO, XX, XY and XXY—to create an agnostic data-driven segmentation of the mouse brain into five distributed clusters which (1) recover fundamental properties of brain organization with high spatial precision, (2) define two previously uncharacterized systems of relative volume excess in females vs. males ("forebrain cholinergic” and "cerebelo-pontine-thalamo-cortical”), and (3) adopt stereotyped spatial motifs which delineate ordered gradients of sex chromosome and gonadal influences on volumetric brain development. Taken together, these data provide a new framework for the study of sexually dimorphic influences on brain development in health and disrupted brain development in SCA. Springer-Verlag (outside the USA), 2014 Brain anatomy nationallicence Sexual dimorphism nationallicence XO nationallicence XXY nationallicence Raznahan Armin Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Rm 4C108, Building 20, 10 Center Drive, 20815, Bethesda, MD, USA aut Lue YanHe Division of Endocrinology, Department of Medicine, Los Angele Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA aut Probst Frank Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA aut Greenstein Deanna Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Rm 4C108, Building 20, 10 Center Drive, 20815, Bethesda, MD, USA aut Giedd Jay Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Rm 4C108, Building 20, 10 Center Drive, 20815, Bethesda, MD, USA aut Wang Christina Division of Endocrinology, Department of Medicine, Los Angele Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA aut Lerch Jason Mouse Imaging Centre and Program in Neuroscience and Mental, The Hospital for Sick Children Hospital, Toronto, ON, Canada aut Swerdloff Ronald Division of Endocrinology, Department of Medicine, Los Angele Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA aut Brain Structure and Function Springer Berlin Heidelberg 220/6(2015-11-01), 3581-3593 1863-2653 220:6<3581 2015 220 429 https://doi.org/10.1007/s00429-014-0875-9 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-014-0875-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Raznahan Armin Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Rm 4C108, Building 20, 10 Center Drive, 20815, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Lue YanHe Division of Endocrinology, Department of Medicine, Los Angele Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA aut NATIONALLICENCE 700 1- Probst Frank Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA aut NATIONALLICENCE 700 1- Greenstein Deanna Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Rm 4C108, Building 20, 10 Center Drive, 20815, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Giedd Jay Child Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Rm 4C108, Building 20, 10 Center Drive, 20815, Bethesda, MD, USA aut NATIONALLICENCE 700 1- Wang Christina Division of Endocrinology, Department of Medicine, Los Angele Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA aut NATIONALLICENCE 700 1- Lerch Jason Mouse Imaging Centre and Program in Neuroscience and Mental, The Hospital for Sick Children Hospital, Toronto, ON, Canada aut NATIONALLICENCE 700 1- Swerdloff Ronald Division of Endocrinology, Department of Medicine, Los Angele Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/6(2015-11-01), 3581-3593 1863-2653 220:6<3581 2015 220 429