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

Jacobus J. Dudok; Alexander J.A. Groffen; Ruud F.T. Toonen; Matthijs Verhage; R.F.G. Toonen

doi:https://doi.org/10.1371/journal.pone.0028137

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

Jacobus J. Dudok, Alexander J.A. Groffen, Ruud F.T. Toonen, Matthijs Verhage, R.F.G. Toonen

Human Genetics (VUmc)

Research output: Contribution to journal › Article › Academic › peer-review

11 Citations (Scopus)

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.

Original language	English
Article number	e28137
Journal	PLOS ONE
Volume	6
Issue number	11
DOIs	https://doi.org/10.1371/journal.pone.0028137
Publication status	Published - 29 Nov 2011

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

https://doi.org/10.1371/journal.pone.0028137

Cite this

@article{bd31f93d466e4425aea43a4fe7f7bde7,

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.",

author = "Dudok, {Jacobus J.} and Groffen, {Alexander J.A.} and Toonen, {Ruud F.T.} and Matthijs Verhage and R.F.G. Toonen",

year = "2011",

month = nov,

day = "29",

doi = "https://doi.org/10.1371/journal.pone.0028137",

language = "English",

volume = "6",

journal = "PLOS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "11",

}

TY - JOUR

T1 - Deletion of Munc18-1 in 5-HT neurons results in rapid degeneration of the 5-HT system and early postnatal lethality

AU - Dudok, Jacobus J.

AU - Groffen, Alexander J.A.

AU - Toonen, Ruud F.T.

AU - Verhage, Matthijs

AU - Toonen, R.F.G.

PY - 2011/11/29

Y1 - 2011/11/29

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=82255173873&partnerID=8YFLogxK

U2 - https://doi.org/10.1371/journal.pone.0028137

DO - https://doi.org/10.1371/journal.pone.0028137

M3 - Article

C2 - 22140524

SN - 1932-6203

VL - 6

JO - PLOS ONE

JF - PLOS ONE

IS - 11

M1 - e28137

ER -

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

Abstract

UN SDGs

Access to Document

Other files and links

Cite this