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and Expression Analysis Core Facility, Department of Biosciences and Nutrition, Karolinska Institute"],"full_dataset_link":["https://www.ebi.ac.uk/ena/browser/view/PRJNA684069"],"scientific_name":["Mus musculus"],"tag":["xref:PubMed:35618883"],"long_description":["Recent studies have identified presynaptic increase in striatal dopamine as the primary dopaminergic abnormality in schizophrenia, responsible for changes in cortical dopamine function in schizophrenic individuals. However, increased dopamine synthesis and release are not recapitulated in existing mouse models, limiting studies on disease progression and potential treatments. We found that the levels of glial cell line-derived neurotrophic factor (GDNF), a strong dopamine system modulator, are increased in the cerebrospinal fluid of first episode psychosis patients. Using a novel strategy to conditionally increase endogenous gene expression, we developed a mouse model with timed elevation of endogenous GDNF. Conditional ‘Knock Up’ of endogenous GDNF expression (GDNF cKU) in the central nervous system at midgestation resulted in an increase of dopamine levels in the presynaptic compartment of nigrostriatal dopamine neurons, hypodopaminergia in the prefrontal cortex (PFC) and schizophrenia-like behavioural deficits in the mouse. RNA sequencing from the PFC revealed gene expression changes similar to those previously found in schizophrenia patients, including downregulation of dopamine receptor 2 and adenosine A2a receptor (A2AR). Treatment of mice with A2AR antagonist istradefylline partially restored striatal and cortical dopamine levels, suggesting a potential therapeutic strategy to alleviate symptoms associated with schizophrenia. Taken together, our results demonstrate that timed increase in GDNF expression is sufficient to drive schizophrenia-like molecular and behavioural phenotypes, and represents a novel model for studying schizophrenia-associated pathologies in mice. Overall design: Transcriptomics analysis from mouse brain. Prefrontal cortex, striatum and substantia nigra were dissected from 2-month-old Nestin-Cre x GDNF cKU mice or from GDNF cKU mice 2 months after striatal AAV-Cre delivery."],"repository":["ENA"],"description_synonyms":["ATF1, ATF2, Glial Cell-Derived Neurotrophic Factor, 3.4.22.-, SCHIZO NEC-CHR/EXACERB, GDNF Growth Factor, Disorders, Glial-Derived, schizophrenia, Laboratory, SCHIZO NEC-SUBCHR/EXACER, Modern, Mus domesticus, HFB1-GDNF, mouse, mini-ICE, CASP-14, Factor, gndf, House Mouse, Glial Derived Neurotrophic Factor, AI385739, unspecified (disorder), Human, schizophrenia with or without an affective disorder, HSCR3, Schizophrenia NOS, unspecified, astrocyte-derived trophic factor, Dementia Praecox, SCHIZO NOS-CHR/EXACERB, Homo sapiens, House, Mus, Other specified types of schizophrenia, Schizophrenic disorders (disorder), SCHIZOPHRENIA NEC-SUBCHR, Mini-ICE, chronic state, SCHIZOPHRENIA NEC-CHR, Schizophrenias, Mus musculus domesticus, unspecified state, Growth Factor, Glial Cell Line Derived Neurotrophic Factor, Glial Cell-Line Derived Neurotrophic Factor, subchronic state with acute exacerbation, Unspecified schizophrenia, subchronic state, Mice, Man, Neurotrophic Factor, Mus musculus., Mus musculus, SCHIZOPHRENIA NEC-UNSPEC, [X]Schizophrenia, Schizophrenia (disorder), Unspecified schizophrenia (disorder), Man (Taxonomy), Caspase-14 subunit p10, Schizophrenic, Swiss, Glial-Derived Neurotrophic Factor, mice, susceptibility to, Swiss Mouse, Schizophrenic disorders, House Mice, Swiss Mice, Caspase-14 subunit p19, Schizophrenic Disorder, Schizophrenia NOS (disorder), MICE, SCZD, Glial Cell Derived Neurotrophic Factor, schizoaffective disorder, Laboratory Mice, domesticus, in remission, Schizophrenic Disorders, Disorder, Modern Man, ATF, chronic state with acute exacerbation, GDNF, Mouse, Glial-Derived Neurotrophic, SCHIZOPHRENIA NOS-UNSPEC, SCHIZOPHRENIA NEC-REMISS, Laboratory Mouse, humans, SCHIZO NOS-SUBCHR/EXACER"],"name_synonyms":["ATF1, ATF2, Glial Cell-Derived Neurotrophic Factor, 3.4.22.-, SCHIZO NEC-CHR/EXACERB, GDNF Growth Factor, Disorders, Glial-Derived, schizophrenia, Laboratory, SCHIZO NEC-SUBCHR/EXACER, Modern, Mus domesticus, HFB1-GDNF, mouse, mini-ICE, CASP-14, Factor, gndf, House Mouse, Glial Derived Neurotrophic Factor, AI385739, unspecified (disorder), Human, schizophrenia with or without an affective disorder, HSCR3, Schizophrenia NOS, unspecified, astrocyte-derived trophic factor, Dementia Praecox, SCHIZO NOS-CHR/EXACERB, Homo sapiens, House, Mus, Other specified types of schizophrenia, Schizophrenic disorders (disorder), SCHIZOPHRENIA NEC-SUBCHR, Mini-ICE, chronic state, SCHIZOPHRENIA NEC-CHR, Schizophrenias, Mus musculus domesticus, unspecified state, Growth Factor, Glial Cell Line Derived Neurotrophic Factor, Glial Cell-Line Derived Neurotrophic Factor, subchronic state with acute exacerbation, Unspecified schizophrenia, subchronic state, Mice, Man, Neurotrophic Factor, Mus musculus., Mus musculus, SCHIZOPHRENIA NEC-UNSPEC, [X]Schizophrenia, Schizophrenia (disorder), Unspecified schizophrenia (disorder), Man (Taxonomy), Caspase-14 subunit p10, Schizophrenic, Swiss, Glial-Derived Neurotrophic Factor, mice, susceptibility to, Swiss Mouse, Schizophrenic disorders, House Mice, Swiss Mice, Caspase-14 subunit p19, Schizophrenic Disorder, Schizophrenia NOS (disorder), MICE, SCZD, Glial Cell Derived Neurotrophic Factor, schizoaffective disorder, Laboratory Mice, domesticus, in remission, Schizophrenic Disorders, Disorder, Modern Man, ATF, chronic state with acute exacerbation, GDNF, Mouse, Glial-Derived Neurotrophic, SCHIZOPHRENIA NOS-UNSPEC, SCHIZOPHRENIA NEC-REMISS, Laboratory Mouse, humans, SCHIZO NOS-SUBCHR/EXACER"],"additional_accession":[]},"is_claimable":false,"name":"Elevated endogenous GDNF levels associate with schizophrenia in humans and mice","description":"Elevated endogenous GDNF levels associate with schizophrenia in humans and mice","dates":{"last_updated":"2025-09-24","first_public":"2023-01-27"},"accession":"PRJNA684069","cross_references":{"GEO":["GSE162974"],"taxon":["10090"],"PubMed":["35618883"]}}