Identification of alternative splicing forms of GLT-1 mRNA in the spinal cord of amyotrophic lateral sclerosis patients

The glutamate transporter plays an essential role in regulating glutamate levels in the synaptic cleft. It has been postulated that the dysfunction of GLT-1, one subtype of glutamate transporter, may be etiologically related to amyotrophic lateral sclerosis (ALS). Two alternative splicing forms of GLT-1 messenger RNA (mRNA) were found in the cervical spinal cord of five ALS patients and three controls. Analysis with reverse transcription-polymerase chain reaction (RT-PCR) showed that the shorter mRNA was a result of exon 8 skipping. A truncated transcript containing an intronic sequence at the 3' end of exon 7 was also demonstrated. However, the incidence of both alternative mRNAs was not different between the five ALS patients and three controls. Interestingly, the mRNA were also found in the cerebral cortex of a, control subject. These results suggest that alternative splicing forms of GLT-1 mRNAs do not play a pathogenetic role in ALS but rather a physiological one in the normal spinal cord and brain. (C) 1998 Elsevier Science Ireland Ltd.