A quantitative regional expression profile of EAAT2 known and novel splice variants reopens the question of aberrant EAAT2 splicing in disease

Tara L. Lauriat, Esther Richler, L. Alison McInnes

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

The glutamate transporter 1 (GLT1) in rodents, or EAAT2 in humans, is alternatively spliced in a complex manner including the use of multiple 5′ and 3′ untranslated regions and several coding variants. We used quantitative RT-PCR to profile these splice variants in human and rat brain. We also used RT-PCR and Northern blotting to demonstrate that a novel isoform of GLT1b has an ∼11 kb 3′ UTR extending through intron 9, exon 10 and approximately 5 kb into the 3′ untranslated region of GLT1. However, our most important finding concerns an aberrant transcript lacking exon 9, which contains a motif permitting translocation from the endoplasmic reticulum. This variant had previously been associated with amyotrophic lateral sclerosis until several groups reported high levels in normal brain tissue. In contrast, our data shows that this aberrant transcript is present at 0.1-0.2% of the major EAAT2 isoforms.

Original languageEnglish
Pages (from-to)271-280
Number of pages10
JournalNeurochemistry International
Volume50
Issue number1
DOIs
StatePublished - Jan 2007

Keywords

  • Alternative splicing
  • EAAT2
  • GLT1
  • Gene expression
  • Quantitative RT-PCR

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