Neonatal lethality of neural crest cell‐specific Rest knockout mice is associated with gastrointestinal distension caused by aberrations of myenteric plexus. (18th August 2014)

• Record Type: Journal Article
• Authors: Aoki, Hitomi; Hara, Akira; Oomori, Yoshiyuki; Shimizu, Yasutake; Yamada, Yasuhiro; Kunisada, Takahiro
• Is Part Of: Genes to cells. Volume 19:Number 10(2014:Oct.)
• Page Start: 723
• Page End: 742
• Publication Date: 2014-08-18
• Subjects: Cytogenetics -- Periodicals; Cells -- Mechanical properties -- Periodicals; Molecular genetics -- Periodicals; Genes -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Biomechanics -- Periodicals; 571.6
• DOI: 10.1111/gtc.12172
• Languages: English
• ISSNs: 1356-9597

Abstract

<abstract abstract-type="main" id="gtc12172-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>RE1‐silencing transcription factor (REST), also known as NRSF (neuron‐restrictive silencer factor), is a well‐known transcriptional repressor of neural genes. <italic>Rest</italic> null mice have embryonic lethality which prevents further investigations of the functions of the <italic>Rest</italic> gene <italic>in vivo</italic>. We studied neonatal but not embryonic lethality that was characterized by gastrointestinal tract dilation in the neural crest cell (NCC)‐specific <italic>Rest</italic> conditional knockout (CKO) mice. While no histological abnormalities except the thinning of the digestive tract as a consequence of the gas accumulation were found in the digestive tract of the mutant mice, they do not have proper gastric retention after oral dye administration and the reduction of acetylcholinesterase (AChE) activity in NCC‐derived myenteric plexus in the stomach was detected. High CO₂ concentration in the dilated digestive tract of the <italic>Rest</italic> CKO mice indicates a failure of gut function by underdeveloped cholinergic transmission in the enteric nervous system. The observed gastrointestinal distension phenotype provides a model for understanding the genetic and molecular basis of NCC defects in humans.</p> </abstract>