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Animal models for studying sex differences

Animal models for studying sex differences. Arthur P. Arnold, PhD Department of Integrative Biology & Physiology Lab of Neuroendocrinology of the Brain Research Institute University of California, Los Angeles (UCLA). UCLA. FCG. LNE. What causes sex differences in physiology and disease?.

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Animal models for studying sex differences

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  1. Animal models for studying sex differences Arthur P. Arnold, PhD Department of Integrative Biology & Physiology Lab of Neuroendocrinology of the Brain Research Institute University of California, Los Angeles (UCLA) UCLA FCG LNE

  2. What causes sex differences in physiology and disease? = F M Possible answers: Gonadal hormones Sex chromosomes Arthur Arnold, "Sex and Gender Differences in Aging" June 6-7, 2019

  3. Arthur Arnold, "Sex and Gender Differences in Aging" June 6-7, 2019

  4. Endocrinology 2005 Arthur Arnold, "Sex and Gender Differences in Aging" June 6-7, 2019

  5. “Four Core Genotypes” (FCG) Mice Paul Burgoyne and Robin Lovell-Badge Make gonadal determination independent of sex chromosome complement to compare XX and XY mice with the same type of gonads XXF XXM XYM XYF Arthur Arnold, "Sex and Gender Differences in Aging" June 6-7, 2019

  6. WT XY male Y-linked Sry is testis-determining. Sry Sry “Four Core Genotypes” (FCG) Mice Sry “moved” to Chromosome 3. Sry 2 kinds of sperm: X or Y - This version of Chrom3 becomes testis-determining. Arthur Arnold, "Sex and Gender Differences in Aging" June 6-7, 2019 4 kinds of sperm: X or XSry or Y or YSry

  7. “Four Core Genotypes” Model XY-(Sry+) father xXX mother abbreviation genome gonads XX XXF offspring: XY- XYF XXM XX(Sry+) XY-(Sry+) XYM Arthur Arnold, "Sex and Gender Differences in Aging" June 6-7, 2019

  8. Sex chromosome complement Four core genotypes Sry+ Gonadal type Sry- Arthur Arnold, "Sex and Gender Differences in Aging" June 6-7, 2019

  9. FCG / phenotypes horm XX=XY investigators no yes Xuqi Chen et al. 2008 neural tube closure defects Midbrain dopamine neurons in vitro Laura Carruth et al. 2002 yes yes XX female XY female Rhonda Voskuhl lab, UCLA yes yes autoimmune disease Arthur Arnold, "Sex and Gender Differences in Aging" June 6-7, 2019

  10. Hormonal and sex chromosome effects on body weight and adiposity 5 months after GDX 40 * 35 day 21 day 45 30 body weight (g) * 25 20 15 10 M M F M F M F M F F F M 5 12 10 7 9 7 12 17 13 10 10 16 12 11 0 XX XY XX XY XX XY Chen et al. PLoS Genet. 2012 Arthur Arnold, "Sex and Gender Differences in Aging" June 6-7, 2019

  11. Interaction of sex hormones and sex chromosomes chow (low fat diet) Chen et al. PLoS Genet. 2012 Arthur Arnold, "Sex and Gender Differences in Aging" June 6-7, 2019

  12. XY* Model: Mice with two X chromosomes are heavier and fatter than mice with one X chromosome Chen et al. PLoS Genet. 2012;8(5):e1002709 Arthur Arnold, "Sex and Gender Differences in Aging" June 6-7, 2019

  13. Inherent sex differences in the genome lead to several types of cellular inequality. Arnold AP. Trends Genet. 2012 28(2):55-61 Arthur Arnold, "Sex and Gender Differences in Aging" June 6-7, 2019

  14. Human X chromosome: Escape from X inactivation 23% of X genes are expressed higher in F than M. NPX PAR F>M tissues M>F X genes Red X escapees are potential drivers of sex differences in cell phenotypes. Tukiainen T et al. Landscape of X chromosome inactivation across human tissues. Nature 2017 550:244-248. Arthur Arnold, "Sex and Gender Differences in Aging" June 6-7, 2019

  15. Where to get sex chromosome mice 1. Ask me. 2. FCG C57BL/6J: Jackson Lab 3. XY* C57BL/6J: UCDavis MMRRC 4. FCG and XY* on different strain backgrounds: Arnold Lab 5. X escapee floxed and knockouts: Gene KO consortia, Arnold lab 6. Transgenes for X escapees and Y gametologs: UCDavis MMRRC Arthur Arnold, "Sex and Gender Differences in Aging" June 6-7, 2019

  16. UCLA Metabolism Lab of Karen Reue Jenny Link Cardiovascular Lab of Mansoureh Eghbali Jingyuan Li, Soban Umar, Christine Cunningham Sex chromosome trisomies, etc. Lab of Eric Vilain Negar Ghahramani, Tuck Ngun Behavior & Cognition Lab of David Jentsch Shawn Aarde Autoimmune Disease: Rhonda Voskuhl Systems Biology: Jake Lusis Feeding Behavior: Yvette Taché Crick Institute, London Paul Burgoyne Robin Lovell-Badge Arnold Lab Xuqi Chen Yuichiro Itoh Shayna Williams-Burris Shawn Aarde Mariam Barseghyan Jessy Martinez Kathy Kampf Rebecca McClusky Maureen Ruiz-Sundstrom Ryan Mackie Haley Hrncir Arthur Arnold, "Sex and Gender Differences in Aging" June 6-7, 2019

  17. Support: thank you! NICHD, ORWH, NIDDK, NHLBI, NINDS, NIMH, NIDCD, OD Society for Women’s Health Research UCLA Iris Cantor Center, CURE, Center for Neurobiology of Stress, Parkinson’s Center Arthur Arnold, "Sex and Gender Differences in Aging" June 6-7, 2019

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