title: Identification of novel GDNF isoforms and cis-antisense GDNFOS gene and their regulation in human middle temporal gyrus of Alzheimer disease.
abstract: 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.
authors.affiliation: Neural Protection and Regeneration Section, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Department of Health and Social Services, Baltimore, Maryland21224, USA.
authors.forename: Mikko
authors.initials: M
authors.lastname: Airavaara
authors.forename: Olga
authors.initials: O
authors.lastname: Pletnikova
authors.forename: Maire E
authors.initials: ME
authors.lastname: Doyle
authors.forename: Yong E
authors.initials: YE
authors.lastname: Zhang
authors.forename: Juan C
authors.initials: JC
authors.lastname: Troncoso
authors.forename: Qing-Rong
authors.initials: QR
authors.lastname: Liu
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D020534:Parahippocampal Gyrus / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D020033:Protein Isoforms; D012333:RNA, Messenger
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