Deletion of Munc18-1 in 5-HT Neurons Results in Rapid Degeneration of the 5-HT System and Early Postnatal Lethality

被引：11
作者：
Dudok, Jacobus J. [1 ]
Groffen, Alexander J. A. [1 ]
Toonen, Ruud F. T. [1 ]
Verhage, Matthijs [1 ]
机构：
[1] Vrije Univ Amsterdam, Dept Funct Genom, CNCR, Amsterdam, Netherlands
来源：
PLOS ONE | 2011年 / 6卷 / 11期
关键词：
SEROTONIN NEURONS; REGULATED SECRETION; BRAIN-SEROTONIN; KNOCKOUT MICE; ABSENCE; INNERVATION;
D O I：
10.1371/journal.pone.0028137
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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.
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页数：6
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