{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:44:37Z","timestamp":1776991477415,"version":"3.51.4"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2015,12,17]],"date-time":"2015-12-17T00:00:00Z","timestamp":1450310400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"DOI":"10.1371\/journal.pgen.1005710","type":"journal-article","created":{"date-parts":[[2015,12,17]],"date-time":"2015-12-17T19:18:57Z","timestamp":1450379937000},"page":"e1005710","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":112,"title":["GDNF Overexpression from the Native Locus Reveals its Role in the Nigrostriatal Dopaminergic System Function"],"prefix":"10.1371","volume":"11","author":[{"given":"Anmol","family":"Kumar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaakko","family":"Kopra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K\u00e4rt","family":"Varendi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauriina L.","family":"Porokuokka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Panhelainen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satu","family":"Kuure","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pepin","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina","family":"Karalija","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mari-Anne","family":"H\u00e4rma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"Vilenius","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kersti","family":"Lillev\u00e4li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Triin","family":"Tekko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jelena","family":"Mijatovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nita","family":"Pulkkinen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madis","family":"Jakobson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maili","family":"Jakobson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roxana","family":"Ola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik","family":"Palm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Lindahl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid","family":"Str\u00f6mberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vootele","family":"V\u00f5ikar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T. Petteri","family":"Piepponen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mart","family":"Saarma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaan-Olle","family":"Andressoo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2015,12,17]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1126\/science.8493557","article-title":"GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons","volume":"260","author":"LF Lin","year":"1993","journal-title":"Science"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/0304-3940(94)90218-6","article-title":"Glial cell line-derived neurotrophic factor reverses toxin-induced injury to midbrain dopaminergic neurons in vivo","volume":"182","author":"BJ Hoffer","year":"1994","journal-title":"Neurosci Lett"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/nrd3430","article-title":"Priorities in Parkinson&apos;s disease research","volume":"10","author":"WG Meissner","year":"2011","journal-title":"Nat Rev Drug Discov"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1006\/exnr.2002.8006","article-title":"Aberrant sprouting and downregulation of tyrosine hydroxylase in lesioned nigrostriatal dopamine neurons induced by long-lasting overexpression of glial cell line derived neurotrophic factor in the striatum by lentiviral gene transfer","volume":"177","author":"B Georgievska","year":"2002","journal-title":"Exp Neurol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"6437","DOI":"10.1523\/JNEUROSCI.1122-04.2004","article-title":"Overexpression of glial cell line-derived neurotrophic factor using a lentiviral vector induces time- and dose-dependent downregulation of tyrosine hydroxylase in the intact nigrostriatal dopamine system","volume":"24","author":"B Georgievska","year":"2004","journal-title":"J Neurosci"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1038\/mt.2009.45","article-title":"Nigrostriatal rAAV-mediated GDNF overexpression induces robust weight loss in a rat model of age-related obesity","volume":"17","author":"FP Manfredsson","year":"2009","journal-title":"Mol Ther"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/nrn812","article-title":"The GDNF family: signalling, biological functions and therapeutic value","volume":"3","author":"MS Airaksinen","year":"2002","journal-title":"Nat Rev Neurosci"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"3136","DOI":"10.1523\/JNEUROSCI.4506-03.2004","article-title":"Regulation of the development of mesencephalic dopaminergic systems by the selective expression of glial cell line-derived neurotrophic factor in their targets","volume":"24","author":"N Kholodilov","year":"2004","journal-title":"J Neurosci"},{"key":"ref9","article-title":"Absolute requirement of GDNF for adult catecholaminergic neuron survival","author":"A Pascual","year":"2008","journal-title":"Nat Neurosci"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/nn.3941","article-title":"GDNF is not required for catecholaminergic neuron survival in vivo","volume":"18","author":"J Kopra","year":"2015","journal-title":"Nat Neurosci"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1471-2199-13-2","article-title":"Characterization of 3&apos;-untranslated region of the mouse GDNF gene","volume":"13","author":"K Oh-Hashi","year":"2012","journal-title":"BMC Mol Biol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/1526-968X(200009)28:1<31::AID-GENE40>3.0.CO;2-K","article-title":"A new positive\/negative selectable marker, puDeltatk, for use in embryonic stem cells","volume":"28","author":"YT Chen","year":"2000","journal-title":"Genesis"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.neuron.2006.02.020","article-title":"Cooperation between GDNF\/Ret and ephrinA\/EphA4 signals for motor-axon pathway selection in the limb","volume":"50","author":"ER Kramer","year":"2006","journal-title":"Neuron"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1126\/science.287.5457.1489","article-title":"Regulation of cell fate decision of undifferentiated spermatogonia by GDNF","volume":"287","author":"X Meng","year":"2000","journal-title":"Science"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/382073a0","article-title":"Defects in enteric innervation and kidney development in mice lacking GDNF","volume":"382","author":"JG Pichel","year":"1996","journal-title":"Nature"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"4077","DOI":"10.1242\/dev.124.20.4077","article-title":"Glial-cell-line-derived neurotrophic factor is required for bud initiation from ureteric epithelium","volume":"124","author":"K Sainio","year":"1997","journal-title":"Development"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1523\/JNEUROSCI.2693-11.2012","article-title":"GDNF Is Predominantly Expressed in the PV+ Neostriatal Interneuronal Ensemble in Normal Mouse and after Injury of the Nigrostriatal Pathway","volume":"32","author":"M Hidalgo-Figueroa","year":"2012","journal-title":"J Neurosci"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/0197-4580(95)02011-X","article-title":"GDNF mRNA expression in normal postnatal development, aging, and in Weaver mutant mice","volume":"16","author":"M Blum","year":"1995","journal-title":"Neurobiol Aging"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"3554","DOI":"10.1523\/JNEUROSCI.17-10-03554.1997","article-title":"Complementary and overlapping expression of glial cell line-derived neurotrophic factor (GDNF), c-ret proto-oncogene, and GDNF receptor-alpha indicates multiple mechanisms of trophic actions in the adult rat CNS","volume":"17","author":"M Trupp","year":"1997","journal-title":"J Neurosci"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jmoldx.2011.08.002","article-title":"RNAscope: a novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues","volume":"14","author":"F Wang","year":"2012","journal-title":"J Mol Diagn"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1002\/syn.20245","article-title":"In heterozygous GDNF knockout mice the response of striatal dopaminergic system to acute morphine is altered","volume":"59","author":"M Airavaara","year":"2006","journal-title":"Synapse"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"4102","DOI":"10.1523\/JNEUROSCI.15-05-04102.1995","article-title":"Amphetamine redistributes dopamine from synaptic vesicles to the cytosol and promotes reverse transport","volume":"15","author":"D Sulzer","year":"1995","journal-title":"J Neurosci"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.pneurobio.2009.11.001","article-title":"Parkinson&apos;s disease: Exit toxins, enter genetics","volume":"90","author":"M Westerlund","year":"2010","journal-title":"Prog Neurobiol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"68","DOI":"10.3389\/fnbeh.2015.00068","article-title":"Nigral proteasome inhibition in mice leads to motor and non-motor deficits and increased expression of Ser129 phosphorylated alpha-synuclein","volume":"9","author":"E Bentea","year":"2015","journal-title":"Front Behav Neurosci"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1111\/j.1471-4159.2010.06918.x","article-title":"Proteasome inhibition in medaka brain induces the features of Parkinson&apos;s disease","volume":"115","author":"H Matsui","year":"2010","journal-title":"J Neurochem"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/0361-9230(94)00224-O","article-title":"Glial cell line-derived neurotrophic factor augments midbrain dopaminergic circuits in vivo","volume":"36","author":"J Hudson","year":"1995","journal-title":"Brain Res Bull"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/S0022-3565(24)36878-8","article-title":"Behavioral and neurochemical effects of intranigral administration of glial cell line-derived neurotrophic factor on aged Fischer 344 rats","volume":"282","author":"MA Hebert","year":"1997","journal-title":"J Pharmacol Exp Ther"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1016\/S0022-3565(25)21275-7","article-title":"Functional effects of GDNF in normal rat striatum: presynaptic studies using in vivo electrochemistry and microdialysis","volume":"279","author":"MA Hebert","year":"1996","journal-title":"J Pharmacol Exp Ther"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0006-8993(96)00683-X","article-title":"Alleviation of behavioral deficits in aged rodents following implantation of encapsulated GDNF-producing fibroblasts","volume":"736","author":"DF Emerich","year":"1996","journal-title":"Brain Res"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1046\/j.1460-9568.2003.02456.x","article-title":"Long-term striatal overexpression of GDNF selectively downregulates tyrosine hydroxylase in the intact nigrostriatal dopamine system","volume":"17","author":"C Rosenblad","year":"2003","journal-title":"Eur J Neurosci"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1186\/2193-1801-3-502","article-title":"Tristetraprolin is a novel regulator of BDNF","volume":"3","author":"A Kumar","year":"2014","journal-title":"Springerplus"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/j.cell.2007.04.040","article-title":"A mammalian microRNA expression atlas based on small RNA library sequencing","volume":"129","author":"P Landgraf","year":"2007","journal-title":"Cell"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"e363","DOI":"10.1371\/journal.pbio.0020363","article-title":"Human MicroRNA targets","volume":"2","author":"B John","year":"2004","journal-title":"PLoS Biol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1261\/rna.2387911","article-title":"MicroRNA transfection and AGO-bound CLIP-seq data sets reveal distinct determinants of miRNA action","volume":"17","author":"J Wen","year":"2011","journal-title":"RNA"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"10898","DOI":"10.1073\/pnas.0504834102","article-title":"The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb","volume":"102","author":"BD Harfe","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ydbio.2005.04.008","article-title":"The role of GDNF in patterning the excretory system","volume":"283","author":"R Shakya","year":"2005","journal-title":"Dev Biol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"5147","DOI":"10.1523\/JNEUROSCI.21-14-05147.2001","article-title":"The role of dopamine receptors in regulating the size of axonal arbors","volume":"21","author":"CL Parish","year":"2001","journal-title":"J Neurosci"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"20049","DOI":"10.1073\/pnas.0706177104","article-title":"RET signaling does not modulate MPTP toxicity but is required for regeneration of dopaminergic axon terminals","volume":"104","author":"S Kowsky","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1159\/000334527","article-title":"Adeno-associated virus type 2 vector-mediated glial cell line-derived neurotrophic factor gene transfer induces neuroprotection and neuroregeneration in a ubiquitin-proteasome system impairment animal model of Parkinson&apos;s disease","volume":"11","author":"Y Du","year":"2013","journal-title":"Neurodegener Dis"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/nm0705-703","article-title":"Glial cell line-derived neurotrophic factor induces neuronal sprouting in human brain","volume":"11","author":"S Love","year":"2005","journal-title":"Nat Med"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1093\/emboj\/19.4.612","article-title":"C-cell hyperplasia, pheochromocytoma and sympathoadrenal malformation in a mouse model of multiple endocrine neoplasia type 2B","volume":"19","author":"CL Smith-Hicks","year":"2000","journal-title":"Embo J"},{"key":"ref42","article-title":"Constitutive Ret signaling is protective for dopaminergic cell bodies but not for axonal terminals","author":"J Mijatovic","year":"2009","journal-title":"Neurobiol Aging"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"4799","DOI":"10.1523\/JNEUROSCI.5647-06.2007","article-title":"Constitutive Ret activity in knock-in multiple endocrine neoplasia type B mice induces profound elevation of brain dopamine concentration via enhanced synthesis and increases the number of TH-positive cells in the substantia nigra","volume":"27","author":"J Mijatovic","year":"2007","journal-title":"J Neurosci"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1111\/j.1471-4159.2008.05265.x","article-title":"Characterization of the striatal dopaminergic neurotransmission in MEN2B mice with elevated cerebral tissue dopamine","volume":"105","author":"J Mijatovic","year":"2008","journal-title":"J Neurochem"},{"key":"ref45","article-title":"From microRNA target validation to therapy: lessons learned from studies on BDNF","author":"K Varendi","year":"2015","journal-title":"Cell Mol Life Sci"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/wrna.121","article-title":"Posttranscriptional upregulation by microRNAs","volume":"3","author":"S Vasudevan","year":"2012","journal-title":"Wiley Interdiscip Rev RNA"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1002\/gene.20111","article-title":"Null and conditional Semaphorin 3B alleles using a flexible puro Delta tk LoxP\/FRT vector","volume":"41","author":"L van der Weyden","year":"2005","journal-title":"Genesis"}],"updated-by":[{"DOI":"10.1371\/journal.pgen.1005808","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2016,1,11]],"date-time":"2016-01-11T00:00:00Z","timestamp":1452470400000}}],"container-title":["PLOS Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pgen.1005710","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,31]],"date-time":"2025-05-31T20:52:48Z","timestamp":1748724768000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1005710"}},"subtitle":[],"editor":[{"given":"Steven","family":"Petrou","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2015,12,17]]},"references-count":47,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2015,12,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1005710","relation":{"correction":[{"id-type":"doi","id":"10.1371\/journal.pgen.1005808","asserted-by":"object"}]},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,12,17]]}}}