Publication: Gastrointestinal phenotype of GAD67lacZ
transgenic mice with early postnatal lethality
Authors
Krecsmarik, M. ; Katarova, Z. ; Bagyánszki, M. ; Szabó, G. ; Fekete, Eva
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
It has been proposed that g-aminobutyric acid
(GABA) in the gut may function as a neurotransmitter,
hormone and/or paracrine agent. Our aim was to
examine transgenic mice of the GAD67-lacZ line with
impaired postnatal growth and early postnatal lethality
for gastrointestinal abnormalities. The gastrointestinal
tract was dissected and processed for histology,
immunohistochemistry, electron microscopy, western
blotting and measurement of GAD activity.
Homozygous mice of both sexes displayed an intestinal
phenotype characterized by a fragile and haemorrhagic
intestinal wall, a reduced number of villi, epithelial
lesions and the occasional appearance of pseudostratified
epithelium. The number of GABA-immunoreactive
enteroendocrine cells and mucin-secreting goblet cells
increased significantly relative to wild-type epithelium.
The appearance of GABA-immunopositive neuronal
perikarya and the lack of GABA-immunoreactive
varicose fibres were observed in the enteric plexuses of
transgenic mice. Tissue homogenates of transgenic mice
showed higher levels of expression of GAD67 and
GAD65 as compared with wild-type mice. Our results
suggest that the possible reason underlying the growth
impairment and postnatal lethality observed in GAD67
transgenic mice is a functional impairment of
GABAergic enteric neurons and disintegration of
intestinal epithelium.
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