Mutation analysis of the human NR4A2 gene, an essential gene for midbrain dopaminergic neurogenesis, in schizophrenic patients

Citation
Yh. Chen et al., Mutation analysis of the human NR4A2 gene, an essential gene for midbrain dopaminergic neurogenesis, in schizophrenic patients, AM J MED G, 105(8), 2001, pp. 753-757
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
AMERICAN JOURNAL OF MEDICAL GENETICS
ISSN journal
0148-7299 → ACNP
Volume
105
Issue
8
Year of publication
2001
Pages
753 - 757
Database
ISI
SICI code
0148-7299(200112)105:8<753:MAOTHN>2.0.ZU;2-U
Abstract
Recent studies have revealed that an orphan receptor gene of the steroid/th yroid hormone nuclear receptor superfamily, the Nurr1 gene, is essential fo r the neurogenesis and differentiation of dopaminergic neurons in the midbr ain of mice. Transgenic mice lacking the Nurr1 gene soon die after birth an d are devoid of dopaminergic neurons in the midbrain. Heterozygous mice sur vive postnatally without obvious locomotor deficits; however, they have inc reased vulnerability to dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-t etrahydropyridine (MPTP). In view of the importance of dopamine neurotransm ission in brain function, we were interested to know if the human homologou s gene of murine Nurr1, the NR4A2 gene, may play a role in the pathogenesis of schizophrenia. We systematically sequenced all the exons of the human N R4A2 gene to search for molecular variants in a cohort of Chinese schizophr enic patients from Taiwan. Two molecular variants were identified: a G-inse rtion in intron 6 (designated IVS6 + 17 similar to +18insG), and a G-deleti on in the untranslated exon 1 (designated c.-469delG). The IVS6 + 17 simila r to + 18insG is a polymorphic one; further case control study, however, di d not reveal association of this polymorphism with schizophrenia. The c.-46 9delG is a rare variant found in two unrelated patients among 177 schizophr enic patients, but not in 130 nonpsychotic controls. The result suggests th at the c.-469delG and possibly other variants of the NR4A2 gene may be of r elevance to the complex factors involved in the pathogenesis of schizophren ia. (C) 2001 Wiley-Liss, Inc.