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A Novel Insect Model To Study The Role Of Fragile X Mental Retardation Protein In Innate Immunity And Behavior

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2019, Doctor of Philosophy, Miami University, Biology.
Fragile X syndrome (FXS) is the most common form of inherited mental retardation and is the primary monogenetic cause of autism spectrum disorders. FXS is caused by a mutation in the regulatory region of the Fragile X Mental Retardation 1 (FMR1) gene, that ultimately leads to loss of the gene product Fragile X Mental Retardation Protein (FMRP). As FXS is a neurodevelopmental disorder, most studies have focused on the role of FMRP during development. However, a few studies have shown that the loss of FMRP during adulthood can impact learning, cognition, and behavior. The primary goal of this study was to decrease FMRP during adulthood and examine the impacts on immune function and social behavior using the cricket Acheta domesticus as a novel insect model. We examined immune function in males and females by assessing several important immune parameters including: the total number of circulating hemocytes in the hemolymph, the total hemolymph protein content, total phenoloxidase enzyme activity, and fat body lysozyme expression. We found that males and females exhibited similar changes in these immune parameters as a result of decreased Fmr1, but males were less likely to survive an immune challenge with an injection of lipopolysaccharide (LPS) from Serratia marcescens. This is the first study to demonstrate that decreased FMRP during adulthood causes sex-specific effects on the immune system. We also examined the effects of decreased Fmr1 on the agonistic behavior of adult male crickets. We observed that the average time to first physical contact during an agonistic interaction was significantly increased in fights between a control male and Fmr1 knockdown male and that Fmr1 knockdown males were less likely to initiate an aggressive interaction than control males. Despite initiating interactions less often, these males fought just as aggressively and won as often as controls. In this study, we also evaluated the parameters required to generate a successful parental RNAi response in the cricket Acheta domesticus. We found that an Fmr1 knockdown could be passed on to the next generation, allowing the cricket to be used for both adult and developmental studies of FXS. This study demonstrates that a decrease in FMRP can have significant impacts on animal physiology and behavior regardless of whether this decrease occurs during development or adulthood.
Kathleen Killian, Dr. (Advisor)
166 p.

Recommended Citations

Citations

  • Sorrell, M. R. (2019). A Novel Insect Model To Study The Role Of Fragile X Mental Retardation Protein In Innate Immunity And Behavior [Doctoral dissertation, Miami University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=miami1564143917001959

    APA Style (7th edition)

  • Sorrell, Mollie. A Novel Insect Model To Study The Role Of Fragile X Mental Retardation Protein In Innate Immunity And Behavior . 2019. Miami University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=miami1564143917001959.

    MLA Style (8th edition)

  • Sorrell, Mollie. "A Novel Insect Model To Study The Role Of Fragile X Mental Retardation Protein In Innate Immunity And Behavior ." Doctoral dissertation, Miami University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=miami1564143917001959

    Chicago Manual of Style (17th edition)