title: Deletion of Munc18-1 in 5-HT neurons results in rapid degeneration of the 5-HT system and early postnatal lethality.
abstract: The serotonin (5-HT) system densely innervates many brain areas and is important for proper brain development. To specifically ablate the 5-HT system we generated mutant mice carrying a floxed Munc18-1 gene and Cre recombinase driven by the 5-HT-specific serotonin reuptake transporter (SERT) promoter. The majority of mutant mice died within a few days after birth. Immunohistochemical analysis of brains of these mice showed that initially 5-HT neurons are formed and the cortex is innervated with 5-HT projections. From embryonic day 16 onwards, however, 5-HT neurons started to degenerate and at postnatal day 2 hardly any 5-HT projections were present in the cortex. The 5-HT system of mice heterozygous for the floxed Munc18-1 allele was indistinguishable from control mice. These data show that deletion of Munc18-1 in 5-HT neurons results in rapid degeneration of the 5-HT system and suggests that the 5-HT system is important for postnatal survival.
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognitive Research (CNCR), Neuroscience Campus Amsterdam, VU University, Amsterdam, The Netherlands.
authors.forename: Jacobus J
authors.initials: JJ
authors.lastname: Dudok
authors.forename: Alexander J A
authors.initials: AJ
authors.lastname: Groffen
authors.forename: Ruud F T
authors.initials: RF
authors.lastname: Toonen
authors.forename: Matthijs
authors.initials: M
authors.lastname: Verhage
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D017353:Gene Deletion; D019426:Integrases / Q000378:metabolism; D051379:Mice; D051938:Munc18 Proteins / Q000378:metabolism*; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology*; D011903:Raphe Nuclei / Q000378:metabolism / Q000473:pathology; D059326:Serotonergic Neurons / Q000378:metabolism* / Q000473:pathology*; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism
chemical_list: D051938:Munc18 Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; C045073:Cre recombinase; D019426:Integrases