PMID- 11340638
OWN - NLM
STAT- MEDLINE
DCOM- 20010719
LR  - 20131121
IS  - 0360-4012 (Print)
IS  - 0360-4012 (Linking)
VI  - 64
IP  - 4
DP  - 2001 May 15
TI  - In vitro regulated expression of tyrosine hydroxylase in ventral midbrain neurons 
      from Nurr1-null mouse pups.
PG  - 322-30
AB  - The transcription factor Nurr1, an orphan member of the steroid-thyroid hormone 
      nuclear receptor superfamily, is essential for the proper terminal 
      differentiation of ventral midbrain dopaminergic neurons. Disruption of the Nurr1 
      gene in mice by homologous recombination abolishes synthesis of dopamine (DA) and 
      expression of DA biosynthetic enzymes, including tyrosine hydroxylase (TH), in 
      the ventral midbrain without affecting the synthesis of DA in other areas of the 
      brain. At birth, however, dopaminergic neuron precursors in Nurr1 null (-/-) pups 
      remain as shown by continued expression of residual, untranslated Nurr1 mRNA not 
      altered by homologous recombination. Since Nurr1 disruption is lethal shortly 
      after birth, to further investigate the developmental properties of these 
      neurons, dissociated ventral midbrain neurons from newborn pups were grown for 5 
      days on an astrocyte feeder layer, subjected to various treatments and then 
      evaluated for expression of TH by fluorescent immunocytochemistry. Initially, a 
      small percentage of neurons (0.26% +/- 0.07%) from the ventral midbrain of Nurr1 
      -/- pups were TH-immunoreactive (TH-IR). No change in TH expression was observed 
      in the presence of glial cell line-derived neurotrophic factor (GDNF), 
      brain-derived neurotrophic factor (BDNF), or DA alone or in combination. 
      Treatment with forskolin (Fsk), however, significantly increased the percentage 
      of TH-IR neurons (1.36% +/- 0.15%). Combination of Fsk, BNDF, and DA further 
      increased the percentage of TH-IR neurons (2.58% +/- 0.50%). Therefore, these 
      data suggest that dopaminergic neuron precursors, which develop in vivo without 
      Nurr1, remain in an undifferentiated condition that is permissive to the 
      induction of TH in vitro. J. Neurosci. Res. 64:322-330, 2001. Published 2001 
      Wiley-Liss, Inc.
FAU - Eells, J B
AU  - Eells JB
AD  - National Institute of Diabetes and Digestive and Kidney Diseases, National 
      Institutes of Health, Bethesda, Maryland 20892, USA.
FAU - Rives, J E
AU  - Rives JE
FAU - Yeung, S K
AU  - Yeung SK
FAU - Nikodem, V M
AU  - Nikodem VM
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cardiotonic Agents)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Gdnf protein, mouse)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Nr4a2 protein, mouse)
RN  - 0 (Nuclear Receptor Subfamily 4, Group A, Member 2)
RN  - 0 (Transcription Factors)
RN  - 1F7A44V6OU (Colforsin)
RN  - EC 1.14.16.2 (Tyrosine 3-Monooxygenase)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Astrocytes/drug effects/metabolism
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cardiotonic Agents/pharmacology
MH  - Cells, Cultured
MH  - Colforsin/*pharmacology
MH  - *DNA-Binding Proteins
MH  - Dopamine/*pharmacology
MH  - Glial Cell Line-Derived Neurotrophic Factor
MH  - Mesencephalon/drug effects/metabolism
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Microtubule-Associated Proteins/metabolism
MH  - *Nerve Growth Factors
MH  - Nerve Tissue Proteins/pharmacology
MH  - Neurons/*drug effects/metabolism
MH  - Neuroprotective Agents/*pharmacology
MH  - Nuclear Receptor Subfamily 4, Group A, Member 2
MH  - Transcription Factors/*deficiency/genetics
MH  - Tyrosine 3-Monooxygenase/*drug effects/metabolism
EDAT- 2001/05/08 10:00
MHDA- 2001/07/20 10:01
CRDT- 2001/05/08 10:00
PHST- 2001/05/08 10:00 [pubmed]
PHST- 2001/07/20 10:01 [medline]
PHST- 2001/05/08 10:00 [entrez]
AID - 10.1002/jnr.1082 [doi]
PST - ppublish
SO  - J Neurosci Res. 2001 May 15;64(4):322-30. doi: 10.1002/jnr.1082.