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Show HEALTH SCIENCES LEAP PROGRAM SPRING 2013 Alexis Gosdis mrsm Naveen Nagarajan HOXB8 GENE MUTATION EFFECTS ON MOUSE MODEL BEHAVIOR Alexis Gosdis (Naveen Nagarajan) Department of Human Genetics University of Utah Grooming is an innate behavior in m a m m a l s . T h e H o x b 8 gene mutation induces excessive grooming behavior in m o u s e models. T h e grooming is so excessive that it leads to hair loss and lesion formation and so is considered pathological. H o x b 8 cell lineage has only been detected in microglia in the brain (Chen et al). Dynamics within and between the microglial cells and other brain cell types m a y be responsible for the excessive grooming behaviors exhibited by the hoxb8 mutant mice. Behavioral analysis apparatus such as the plus maze, LABORAS, and open field test were used to examine differences in behaviors between the mutant and wild type mice. They have s h o w n that hoxb8 mutants spend a significantly larger a m o u n t of time grooming than their wild-type counterparts. T h e mutants have also s h o w n an element of heightened anxiety compared to the wild-type mice. Immunohistochemistry along with IMARIS software were used to count the number of microglia, examine its morphological structure, and examine its influences on surrounding structures. Colocolization of G F P and Td-tomato suggests there are t w o populations of microglia, those expressing hoxb8 and those that are not. T h e subpopulation with hoxb8 accounts for 4 0 % of microglia. We propose there is an OCD circuit, which encompasses neural connections between orbito-frontal areas, caudate and p u t a m e n areas and pre frontal areas based on h u m a n studies on O C D . T h e dynamics of Feed forward and feed back connectivities might play an important role in developing O C D phenotype. W e suggest that there m a y b e s o m e alterations in these connections via Hoxb8mutation, although further examination is required. Mechanisms are u n k n o w n as to what areas of the brain initiate and/or sustain grooming behavior; though, it can be inferred that hoxb8 microglia play a significant role in influencing neuronal activity and inducing the connectivity and neural circuit changes. |