Dopamine neuron agenesis in Nurr1-deficient mice.
Dopamine neurons of the substantia nigra and ventral tegmental area regulate movement and affective behavior and degenerate in Parkinson's disease. The orphan nuclear receptor Nurr1 was shown to be expressed in developing dopamine neurons before the appearance of known phenotypic markers for these cells. Mice lacking Nurr1 failed to generate midbrain dopaminergic neurons, were hypoactive, and died soon after birth. Nurr1 expression continued into adulthood, and brains of heterozygous animals, otherwise apparently healthy, contained reduced dopamine levels. These results suggest that putative Nurr1 ligands may be useful for treatment of Parkinson's disease and other disorders of midbrain dopamine circuitry.
Zetterström
R H
RH
Department of Neuroscience, Karolinska Institute, S-171 77 Stockholm, Sweden.
Solomin
L
L
Jansson
L
L
Hoffer
B J
BJ
Olson
L
L
Perlmann
T
T
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism; D004268:DNA-Binding Proteins; D004298:Dopamine / Q000096:biosynthesis / Q000378:metabolism*; D018390:Gene Targeting; D006579:Heterozygote; D008024:Ligands; D008636:Mesencephalon / Q000002:abnormalities / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D008024:Ligands; D009419:Nerve Tissue Proteins; C539883:Nr4a2 protein, mouse; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D012333:RNA, Messenger; D014157:Transcription Factors; D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine