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Altered Isoform Expression of the Serotonin 2C Receptor Disrupts Normal Maternal Care

dc.creatorJacobs, Michelle Marie
dc.description.abstractRNA 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.
dc.subjectG-protein coupling
dc.subjectadaptive compensation
dc.subjectRNA editing
dc.subjectconstitutive activity
dc.subjectSerotonin -- Receptors
dc.subjectSerotonin -- Physiological effect
dc.subjectParental behavior in animals
dc.titleAltered Isoform Expression of the Serotonin 2C Receptor Disrupts Normal Maternal Care
dc.contributor.committeeMemberRandy Blakely
dc.contributor.committeeMemberElaine Sanders-Bush
dc.contributor.committeeMemberMaureen Gannon
dc.contributor.committeeMemberRonald Emeson
dc.type.materialtext University
dc.contributor.committeeChairPat Levitt

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