This application for an administrative supplement to NIH Grant U42 OD012210, the parent grant of the Mutant Mouse Resource and Research Center (MMRRC) at UC Davis, is submitted in response to NOT-OD-20-049 Notice of Special Interest: Administrative Supplements for Research on Sex/Gender Influences. This supplement will address the first of five objectives of the 2019-2023 Trans-NIH Strategic Plan for Women?s Health Research ?Advancing Science for the Health of Women?: Advancing rigorous research that is relevant to the health of women. This application proposes pre-clinical research using mouse models of patient-specific genomic variants as one of three sex-based study types, and includes two of the three proscribed sex-based research approaches: addition of the opposite sex (in this case, female) and increasing sample size. To do so, we will conduct the following 3 specific aims: 1) generate cohorts of female mice for variants nominated from male patients; 2) conduct in vivo targeted phenotyping of female cohorts of mice; and 3) promote awareness and availability of genetic variants in female mouse models. We propose to study the pathophysiological consequences of genetic variation in female mice for up to 10 genomic variants we have already studied in male mice. The purpose of the proposed preclinical research project is to increase mechanistic understanding of sex differences in phenotypic expression of genetic variants using comparative studies of male and female physiological systems in mice.

Public Health Relevance

This proposal from the Mutant Mouse Resource and Research Center at UC Davis (MMRRC-UC Davis) intends to address areas of need in preclinical research that are outlined in the 2019-2023 Trans-NIH Strategic Plan for Women?s Health Research ?Advancing Science for the Health of Women?. Specifically, by studying the pathophysiological consequences of human genetic variation in female mice, we will increase mechanistic understanding of sex differences in phenotypic expression of genetic variants in humans. Further, because adhering to high standards of scientific rigor is critical for generating reproducible results, the research we propose has been rigorously designed, including consideration of the influences of sex, and will contribute to the NIH agenda to promote research that seeks to improve the health of women.

National Institute of Health (NIH)
Office of The Director, National Institutes of Health (OD)
Animal (Mammalian and Nonmammalian) Model, and Animal and Biological Materials Resource Cooperative Agreements (U42)
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Special Emphasis Panel (ZRG1)
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Mirochnitchenko, Oleg
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University of California Davis
Schools of Medicine
United States
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Shin, Sora; Pribiag, Horia; Lilascharoen, Varoth et al. (2018) Drd3 Signaling in the Lateral Septum Mediates Early Life Stress-Induced Social Dysfunction. Neuron 97:195-208.e6
Valero-Jiménez, Ana; Zúñiga, Joaquín; Cisneros, José et al. (2018) Transmembrane protease, serine 4 (TMPRSS4) is upregulated in IPF lungs and increases the fibrotic response in bleomycin-induced lung injury. PLoS One 13:e0192963
Jeong, Yeongseok; Huh, Namjung; Lee, Joonyeup et al. (2018) Role of the hippocampal CA1 region in incremental value learning. Sci Rep 8:9870
Hoerder-Suabedissen, Anna; Hayashi, Shuichi; Upton, Louise et al. (2018) Subset of Cortical Layer 6b Neurons Selectively Innervates Higher Order Thalamic Nuclei in Mice. Cereb Cortex 28:1882-1897
Lanjakornsiripan, Darin; Pior, Baek-Jun; Kawaguchi, Daichi et al. (2018) Layer-specific morphological and molecular differences in neocortical astrocytes and their dependence on neuronal layers. Nat Commun 9:1623
Tröster, Philip; Haseleu, Julia; Petersen, Jonas et al. (2018) The Absence of Sensory Axon Bifurcation Affects Nociception and Termination Fields of Afferents in the Spinal Cord. Front Mol Neurosci 11:19
Gelegen, Cigdem; Miracca, Giulia; Ran, Mingzi Z et al. (2018) Excitatory Pathways from the Lateral Habenula Enable Propofol-Induced Sedation. Curr Biol 28:580-587.e5
Ralvenius, William T; Neumann, Elena; Pagani, Martina et al. (2018) Itch suppression in mice and dogs by modulation of spinal ?2 and ?3GABAA receptors. Nat Commun 9:3230
McCullough, Kenneth M; Daskalakis, Nikolaos P; Gafford, Georgette et al. (2018) Cell-type-specific interrogation of CeA Drd2 neurons to identify targets for pharmacological modulation of fear extinction. Transl Psychiatry 8:164
Chen, Li; Chen, Ruju; Kemper, Sherri et al. (2018) Therapeutic effects of serum extracellular vesicles in liver fibrosis. J Extracell Vesicles 7:1461505

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