Identification of novel GDNF isoforms and cis-antisense GDNFOS gene and their regulation in human middle temporal gyrus of Alzheimer disease

J Biol Chem. 2011 Dec 30;286(52):45093-102. doi: 10.1074/jbc.M111.310250. Epub 2011 Nov 11.


Primate-specific genes and isoforms could provide insight into human brain diseases. Our bioinformatic analysis revealed that there are possibly five isoforms of human GDNF gene with different pre- and pro-regions by inter- and intra-exon splicing. By using TaqMan primer probe sets, designed between exons, we verified the expression of all isoforms. Furthermore, a novel GDNFOS gene was found to be transcribed from the opposite strand of GDNF gene. GDNFOS gene has four exons that are spliced into different isoforms. GDNFOS1 and GDNFOS2 are long noncoding RNAs, and GDNFOS3 encodes a protein of 105 amino acids. To study human GDNF and GDNFOS regulation in neurodegenerative diseases, the protein and mRNA levels were measured by Western blot and RT-quantitative PCR, respectively, in postmortem middle temporal gyrus (MTG) of Alzheimer disease (AD) and Huntington disease (HD) patients in comparison with those of normal controls. In the MTG of AD patients, the mature GDNF peptide was down-regulated; however, the transcript of GDNF isoform from human exon 2 was up-regulated, whereas that of the conserved isoform from exon 1 remained unchanged in comparison with those of normal controls. In contrast, the mature GDNF peptide and the isoform mRNA levels were not changed in the MTG of HD. The findings of novel GDNF and GDNFOS isoforms and differences in tissue expression patterns dysregulated in AD brains may further reveal the role of endogenous GDNF in human brain diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Animals
  • Base Sequence
  • Exons / genetics
  • Gene Expression Regulation*
  • Glial Cell Line-Derived Neurotrophic Factor / biosynthesis*
  • Glial Cell Line-Derived Neurotrophic Factor / genetics
  • Humans
  • Huntington Disease / genetics
  • Huntington Disease / metabolism
  • Huntington Disease / pathology
  • Male
  • Molecular Sequence Data
  • Parahippocampal Gyrus / metabolism*
  • Parahippocampal Gyrus / pathology
  • Protein Isoforms / biosynthesis
  • Protein Isoforms / genetics
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley


  • Glial Cell Line-Derived Neurotrophic Factor
  • Protein Isoforms
  • RNA, Messenger

Associated data

  • GENBANK/JF824129
  • GENBANK/JF824130
  • GENBANK/JF824131