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Title page for ETD etd-01192009-142814

Type of Document Dissertation
Author Jacobs, Michelle Marie
URN etd-01192009-142814
Title Altered Isoform Expression of the Serotonin 2C Receptor Disrupts Normal Maternal Care
Degree PhD
Department Neuroscience
Advisory Committee
Advisor Name Title
Pat Levitt Committee Chair
Elaine Sanders-Bush Committee Member
Maureen Gannon Committee Member
Randy Blakely Committee Member
Ronald Emeson Committee Member
  • G-protein coupling
  • adaptive compensation
  • RNA editing
  • constitutive activity
  • Serotonin -- Receptors
  • Serotonin -- Physiological effect
  • Parental behavior in animals
Date of Defense 2008-03-11
Availability unrestricted
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.
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