RNA transcripts encoding the 2C-subtype of the serotonin (5HT2C) receptor are modified by adenosine-to-inosine editing events to generate as many as twenty-four 5HT2C receptor protein isoforms. These modified receptors are expressed in a region-specific manner in the central nervous system (CNS) and demonstrate differences in their constitutive activity and efficacy to interact with specific G-proteins. To determine the physiologic relevance of 5HT2C RNA editing, I generated mutant mice solely expressing the non-edited isoform (5HT2C-INI) of the receptor. Heterozygous mutant dams display profound behavioral deficits in maternal care including poor nest formation and altered pup retrieval that affect growth and anxiety-related behavior in both wild-type and mutant offspring. Treatment with a selective 5HT2C inverse agonist rescues deficits in pup retrieval, indicating that altered 5HT2C signaling underlies the observed alterations in maternal behavior. These studies not only indicate a role for 5HT2C signaling in maternal care, but also demonstrate the importance of normal patterns of 5HT2C RNA editing in vivo.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-01192009-142814 |
| Date | 20 January 2009 |
| Creators | Jacobs, Michelle Marie |
| Contributors | Randy Blakely, Pat Levitt, Elaine Sanders-Bush, Maureen Gannon, Ronald Emeson |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-01192009-142814/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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