Skip to main contentSkip to search and navigation

UEF eREPOSITORY

    • English
    • suomi
  • English 
    • English
    • suomi
  • Login
View Item 
  •   Home
  • Artikkelit
  • Terveystieteiden tiedekunta
  • View Item
  •   Home
  • Artikkelit
  • Terveystieteiden tiedekunta
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Loss of Cln5 leads to altered Gad1 expression and deficits in interneuron development in mice

Thumbnail
Files
Article (2.626Mb)
Self archived version
final draft
Date
2019
Author(s)
Singh, Y
Leinonen, H
Fazaludeen, F
Jaronen, M
Guest, D
Buckley, N
Byts, N
Oksa, P
Jalkanen, K
Iqbal, I
Huuskonen, M
Savchenko, E
Keksa-Goldsteine, V
Chew, S
Myllyharju, J
Tanila, H
Ooi, L
Koistinaho, J
Kanninen, KM
Malm, T
Unique identifier
10.1093/hmg/ddz165
Metadata
Show full item record
More information
Research Database SoleCris

Self-archived article

Citation
Singh, Y. Leinonen, H. Fazaludeen, F. Jaronen, M. Guest, D. Buckley, N. Byts, N. Oksa, P. Jalkanen, K. Iqbal, I. Huuskonen, M. Savchenko, E. Keksa-Goldsteine, V. Chew, S. Myllyharju, J. Tanila, H. Ooi, L. Koistinaho, J. Kanninen, KM. Malm, T. (2019). Loss of Cln5 leads to altered Gad1 expression and deficits in interneuron development in mice.  Human molecular genetics, 28 (11) , 3309-3322. 10.1093/hmg/ddz165.
Rights
© Oxford University Press
Licensed under
All rights reserved
Abstract

The Finnish-variant late infantile neuronal ceroid lipofuscinosis, also known as CLN5 disease, is caused by mutations in the CLN5 gene. Cln5 is strongly expressed in the developing brain and expression continues into adulthood. CLN5, a protein of unknown function, is implicated in neurodevelopment but detailed investigation is lacking. Using Cln5−/− embryos of various ages and cells harvested from Cln5−/− brains we investigated the hitherto unknown role of Cln5 in the developing brain. Loss of Cln5 results in neuronal differentiation deficits and delays in interneuron development during in utero period. Specifically, the radial thickness of dorsal telencephalon was significantly decreased in Cln5−/− mouse embryos at embryonic day 14.5 (E14.5), and expression of Tuj1, an important neuronal marker during development, was down-regulated. An interneuron marker calbindin and a mitosis marker p-H3 showed down-regulation in ganglionic eminences. Neurite outgrowth was compromised in primary cortical neuronal cultures derived from E16 Cln5−/− embryos compared with WT embryos. We show that the developmental deficits of interneurons may be linked to increased levels of the repressor element 1-silencing transcription factor, which we report to bind to glutamate decarboxylase (Gad1), which encodes GAD67, a rate-limiting enzyme in the production of gamma-aminobutyric acid (GABA). Indeed, adult Cln5−/− mice presented deficits in hippocampal parvalbumin-positive interneurons. Furthermore, adult Cln5−/− mice presented deficits in hippocampal parvalbumin-positive interneurons and showed age-independent cortical hyper excitability as measured by electroencephalogram and auditory-evoked potentials. This study highlights the importance of Cln5 in neurodevelopment and suggests that in contrast to earlier reports, CLN5 disease is likely to develop during embryonic stages.

Subjects
stem cells   electroencephalography   gamma-aminobutyric acid   adult   embryo   genes   interneurons   brain   mice   neuronal outgrowth   
URI
https://erepo.uef.fi/handle/123456789/7934
Link to the original item
http://dx.doi.org/10.1093/hmg/ddz165
Publisher
Oxford University Press (OUP)
Collections
  • Terveystieteiden tiedekunta [1324]
University of Eastern Finland
OpenAccess
eRepo
erepo@uef.fi
OpenUEF
Service provided by
the University of Eastern Finland Library
Library web pages
Twitter
Facebook
Youtube
Library blog
 sitemap
Search

Browse

All of the ArchiveResource types & CollectionsBy Issue DateAuthorsTitlesSubjectsFacultyDepartmentFull organizationSeriesMain subjectThis CollectionBy Issue DateAuthorsTitlesSubjectsFacultyDepartmentFull organizationSeriesMain subject

My Account

Login
University of Eastern Finland
OpenAccess
eRepo
erepo@uef.fi
OpenUEF
Service provided by
the University of Eastern Finland Library
Library web pages
Twitter
Facebook
Youtube
Library blog
 sitemap