cDNA sequence and differential mRNA regulation of two forms of glial cell line-derived neurotrophic factor in Schwann cells and rat skeletal muscle

Joe E. Springer, Jeffrey L. Seeburger, H. E. Jin, Ana Gabrea, Elizabeth P. Blankenhorn, Lawrence W. Bergman

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

Total RNA from rat Schwann cells grown in culture and adult rat skeletal muscle was reverse transcribed, amplified for glial cell line-derived neurotrophic factor (GDNF) messenger RNA (mRNA) using the polymerase chain reaction (PCR), and the PCR products sequenced. Two forms of GDNF were detected in the PCR step, one of a predicted size (GDNF633) and a second smaller form missing a 78-base pair sequence (GDNF555). Sequence analysis demonstrated that GDNF633 is similar to the published sequence of GDNF differing only at three nucleotides. Southern and Northern blot analyses reveal that the two forms are probably derived from a single RNA species that is alternatively spliced. Interestingly, (GDNF633) mRNA was found to be selectively upregulated in denervated rat skeletal muscle at 1-2 weeks following axotomy, providing evidence that the innervation status of the muscle may determine the expression profile of the two alternately spliced forms. Given these findings, we suggest that GDNF may function as a target-derived trophic factor for neuronal populations innervating skeletal muscle, including sensory neurons and spinal cord motoneurons.

Original languageEnglish
Pages (from-to)47-52
Number of pages6
JournalExperimental Neurology
Volume131
Issue number1
DOIs
StatePublished - Jan 1995

Bibliographical note

Funding Information:
We thank L. Teny for her excellent technical assistance, Dr. Ann Graybiel for a critical review of this manuscript, and Dr. Timothy Collier for the primary Schwann ceII cultures. This study was supported in part by NIH Grants AGO8969 and NS30502 and the AIzheimer’s Research Center at Hahnemann (J.E.S.).

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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