TY  - JOUR
A1  - Song, Ning-Ning
A1  - Xiu, Jian-Bo
A1  - Huang, Ying
A1  - Chen, Jia-Yin
A1  - Zhang, Lei
A1  - Gutknecht, Lise
A1  - Lesch, Klaus Peter
A1  - Li, He
A1  - Ding, Yu-Qiang
T1  - Adult Raphe-Specific Deletion of Lmx1b Leads to Central Serotonin Deficiency
JF  - PLoS ONE
N2  - The transcription factor Lmx1b is essential for the differentiation and survival of central serotonergic (5-HTergic) neurons during embryonic development. However, the role of Lmx1b in adult 5-HTergic neurons is unknown. We used an inducible Cre-LoxP system to selectively inactivate Lmx1b expression in the raphe nuclei of adult mice. Pet1-CreER(T2) mice were generated and crossed with Lmx1b(flox/flox) mice to obtain Pet1-CreER(T2); Lmx1b(flox/flox) mice (which termed as Lmx1b iCKO). After administration of tamoxifen, the level of 5-HT in the brain of Lmx1b iCKO mice was reduced to 60% of that in control mice, and the expression of tryptophan hydroxylase 2 (Tph2), serotonin transporter (Sert) and vesicular monoamine transporter 2 (Vmat2) was greatly down-regulated. On the other hand, the expression of dopamine and norepinephrine as well as aromatic L-amino acid decarboxylase (Aadc) and Pet1 was unchanged. Our results reveal that Lmx1b is required for the biosynthesis of 5-HT in adult mouse brain, and it may be involved in maintaining normal functions of central 5-HTergic neurons by regulating the expression of Tph2, Sert and Vmat2.
KW  - Molecular-genetics
KW  - Sonic hedgehog
KW  - Neurons
KW  - Mice
KW  - Brain
KW  - Expression
KW  - System
KW  - PET-1
KW  - Transporter
KW  - Disorders
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133581
VL  - 6
IS  - 1
ER  - 
TY  - JOUR
A1  - Haddad, Dana
A1  - Chen, Nanhai G.
A1  - Zhang, Qian
A1  - Chen, Chun-Hao
A1  - Yu, Yong A.
A1  - Gonzalez, Lorena
A1  - Carpenter, Susanne G.
A1  - Carson, Joshua
A1  - Au, Joyce
A1  - Mittra, Arjun
A1  - Gonen, Mithat
A1  - Zanzonico, Pat B.
A1  - Fong, Yuman
A1  - Szalay, Aladar A.
T1  - Insertion of the human sodium iodide symporter to facilitate deep tissue imaging does not alter oncolytic or replication capability of a novel vaccinia virus
JF  - Journal of Translational Medicine
N2  - Introduction: 

Oncolytic viruses show promise for treating cancer. However, to assess therapeutic efficacy and potential toxicity, a noninvasive imaging modality is needed. This study aimed to determine if insertion of the human sodium iodide symporter (hNIS) cDNA as a marker for non-invasive imaging of virotherapy alters the replication and oncolytic capability of a novel vaccinia virus, GLV-1h153. 

Methods: 

GLV-1h153 was modified from parental vaccinia virus GLV-1h68 to carry hNIS via homologous recombination. GLV-1h153 was tested against human pancreatic cancer cell line PANC-1 for replication via viral plaque assays and flow cytometry. Expression and transportation of hNIS in infected cells was evaluated using Westernblot and immunofluorescence. Intracellular uptake of radioiodide was assessed using radiouptake assays. Viral cytotoxicity and tumor regression of treated PANC-1tumor xenografts in nude mice was also determined. Finally, tumor radiouptake in xenografts was assessed via positron emission tomography (PET) utilizing carrier-free (124)I radiotracer. 

Results: 

GLV-1h153 infected, replicated within, and killed PANC-1 cells as efficiently as GLV-1h68. GLV-1h153 provided dose-dependent levels of hNIS expression in infected cells. Immunofluorescence detected transport of the protein to the cell membrane prior to cell lysis, enhancing hNIS-specific radiouptake (P < 0.001). In vivo, GLV-1h153 was as safe and effective as GLV-1h68 in regressing pancreatic cancer xenografts (P < 0.001). Finally, intratumoral injection of GLV-1h153 facilitated imaging of virus replication in tumors via (124)I-PET. 

Conclusion: 

Insertion of the hNIS gene does not hinder replication or oncolytic capability of GLV-1h153, rendering this novel virus a promising new candidate for the noninvasive imaging and tracking of oncolytic viral therapy.
KW  - Human Sodium/Iodide symporter
KW  - Reporter gene
KW  - NA+/I-symporter
KW  - Nude-mice
KW  - Cancer
KW  - In-Vivo
KW  - Expression
KW  - Therapy
KW  - Transporter
KW  - GLV-1H68
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-140847
VL  - 9
IS  - 36
ER  -