PMID- 12153483
OWN - NLM
STAT- MEDLINE
DCOM- 20020830
LR  - 20190630
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 82
IP  - 3
DP  - 2002 Aug
TI  - Alternative splicing of the 5'-sequences of the mouse EAAT2 glutamate transporter 
      and expression in a transgenic model for amyotrophic lateral sclerosis.
PG  - 594-603
AB  - Glutamate-mediated neurotoxicity and a reduced expression of the excitatory amino 
      acid transporter 2 (EAAT2) have been described in the pathogenesis of several 
      acute and chronic neurological conditions. EAAT2 is the major carrier of 
      glutamate in the mammalian brain. However, the principles of EAAT2 expression 
      regulation are not fully understood. For the human brain, extensive alternative 
      splicing of the EAAT2 RNA has been shown. To delineate the complex RNA regulation 
      of EAAT2 we investigated whether the murine species is a suitable model for the 
      study of EAAT2 splicing events. We identified five splice variants 
      (mEAAT2/5UT1-5) encoding different 5'-untranslated sequences and two distinct 
      N-termini of the putative EAAT2 polypeptide. In the murine CNS we found a 
      region-specific expression pattern of the novel 5'-variants of EAAT2 as shown by 
      in situ hybridization, dot blotting and competitive reverse transcription 
      polymerase chain reaction. Furthermore, we performed an expression analysis of 
      the EAAT2 splice variants in the spinal cord of a transgenic model (SOD1G93A) of 
      amyotrophic lateral sclerosis, a motor neurone disease for which altered splicing 
      of EAAT2 has been discussed. We found an increased expression of mEAAT2/5UT4 and 
      a reduction of mEAAT2/5UT5 in the early course of the disease. We conclude that 
      alternative splicing of 5'-sequences may contribute to the regional expression of 
      the EAAT2 RNA and was altered in the pre-symptomatic stage of the SOD1G93A-mouse 
      model for amyotrophic lateral sclerosis.
FAU - Munch, C
AU  - Munch C
AD  - Department of Neurology, University of Ulm, Germany.
FAU - Ebstein, M
AU  - Ebstein M
FAU - Seefried, U
AU  - Seefried U
FAU - Zhu, B
AU  - Zhu B
FAU - Stamm, S
AU  - Stamm S
FAU - Landwehrmeyer, G B
AU  - Landwehrmeyer GB
FAU - Ludolph, A C
AU  - Ludolph AC
FAU - Schwalenstocker, B
AU  - Schwalenstocker B
FAU - Meyer, T
AU  - Meyer T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Excitatory Amino Acid Transporter 2)
RN  - EC 1.15.1.1 (SOD1 G93A protein)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
SB  - IM
MH  - 5' Untranslated Regions/*genetics
MH  - *Alternative Splicing
MH  - Amyotrophic Lateral Sclerosis/genetics/*metabolism
MH  - Animals
MH  - Base Sequence
MH  - Brain/metabolism
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Excitatory Amino Acid Transporter 2/*genetics/metabolism
MH  - Gene Expression Regulation
MH  - Hippocampus/metabolism
MH  - Humans
MH  - In Situ Hybridization
MH  - Mice
MH  - Mice, Transgenic
MH  - Molecular Sequence Data
MH  - Organ Specificity
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Spinal Cord/metabolism
MH  - Superoxide Dismutase/genetics
EDAT- 2002/08/03 10:00
MHDA- 2002/08/31 10:01
CRDT- 2002/08/03 10:00
PHST- 2002/08/03 10:00 [pubmed]
PHST- 2002/08/31 10:01 [medline]
PHST- 2002/08/03 10:00 [entrez]
AID - 1012 [pii]
AID - 10.1046/j.1471-4159.2002.01012.x [doi]
PST - ppublish
SO  - J Neurochem. 2002 Aug;82(3):594-603. doi: 10.1046/j.1471-4159.2002.01012.x.