Deletion of Munc18-1 in 5-HT neurons results in rapid degeneration of the 5-HT system and early postnatal lethality

PLoS One. 2011;6(11):e28137. doi: 10.1371/journal.pone.0028137. Epub 2011 Nov 29.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Gene Deletion*
  • Integrases / metabolism
  • Mice
  • Munc18 Proteins / metabolism*
  • Nerve Degeneration / metabolism*
  • Nerve Degeneration / pathology*
  • Raphe Nuclei / metabolism
  • Raphe Nuclei / pathology
  • Serotonergic Neurons / metabolism*
  • Serotonergic Neurons / pathology*
  • Serotonin / metabolism*
  • Serotonin Plasma Membrane Transport Proteins / metabolism

Substances

  • Munc18 Proteins
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin
  • Cre recombinase
  • Integrases