INT151168

Context Info Confidence 0.78 First Reported 2003 Last Reported 2011 Negated 0 Speculated 0 Reported most in Body Documents 60 Total Number 61 Disease Relevance 35.63 Pain Relevance 10.54

phosphatase activity (Pten) mitochondrion (Pten) plasma membrane (Pten) nucleus (Pten) intracellular (Pten) enzyme binding (Pten)

Anatomy Link Frequency DA neurons 6 muscle 4 skeletal muscle 3 brain 2 striatum 2 Pten (Mus musculus)

Pain Link Frequency Relevance Heat Clonidine 4 100.00 Dopamine 2185 99.84 rheumatoid arthritis 274 99.80 metalloproteinase 128 99.30 Substantia nigra 152 98.68 agonist 95 98.64 Catecholamine 19 98.60 Nucleus accumbens 19 97.32 midbrain 285 97.24 Ventral tegmentum 152 97.10

Disease Link Frequency Relevance Heat Cancer 1167 100.00 Apoptosis 562 100.00 Targeted Disruption 404 100.00 Disease 353 100.00 Rheumatoid Arthritis 278 99.80 Autism 10 99.78 Adenocarcinoma 245 99.68 Prostate Cancer 16 99.64 Hepatocellular Cancer 113 99.60 Hypertrophy 252 99.24

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Suppressing PTEN expression protects DA neurons against exposure to a neurotoxin

Gene_expression (expression) of PTEN in DA neurons associated with dopamine

1) Confidence 0.78 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2736587 Disease Relevance 0.15 Pain Relevance 0.34

Mice lacking PTEN expression in DA cells showed an increase in catecholamine content in both the midbrain containing the DA cell bodies (fig. 6D) and in the terminal region in the dorsal striatum (fig. 6B).

Gene_expression (expression) of PTEN in striatum associated with dopamine, catecholamine and midbrain

2) Confidence 0.78 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2736587 Disease Relevance 0 Pain Relevance 1.01

Even though we looked at 5 mouse strains, it is still possible that the disparity in PTEN expression is the result of differences in the background strain of the transgenic line.

Gene_expression (expression) of PTEN associated with targeted disruption and sprains and strains

3) Confidence 0.69 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2905373 Disease Relevance 0.69 Pain Relevance 0

It is interesting to note that even though skeletal muscle is highly insulin sensitive and has a low incidence of transformation, PTEN is expressed at a substantially lower level in skeletal muscle than any other tissue analysed.

Gene_expression (expressed) of PTEN in skeletal muscle

4) Confidence 0.69 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2905373 Disease Relevance 0.17 Pain Relevance 0

PTEN is widely distributed in the brain and is preferentially expressed in neurons, where it localizes to both the nucleus and cytoplasm [4]–[7].

Gene_expression (expressed) of PTEN in neurons

5) Confidence 0.68 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2736587 Disease Relevance 1.19 Pain Relevance 0

The relationship between PTEN and Parkinson’s disease has been emphasized in several studies often in reference to mitochondrial function.

Gene_expression (disease) of PTEN associated with disease

6) Confidence 0.67 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2736587 Disease Relevance 0.22 Pain Relevance 0.30

Interestingly, PTEN ablation did not generate changes in TH optical density in the striatum or nucleus accumbens, suggesting an equal distribution of dopaminergic terminals between Pten KO and control animals.

Gene_expression (ablation) of PTEN in nucleus accumbens associated with nucleus accumbens

7) Confidence 0.67 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2736587 Disease Relevance 0.29 Pain Relevance 0.50

The effects of PTEN deletion in DA neurons, as well as postsynaptic regions will be discussed in detail below.

Gene_expression (deletion) of PTEN in DA neurons associated with dopamine

8) Confidence 0.67 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2736587 Disease Relevance 0.29 Pain Relevance 0.46

In a previous report we first detected DAT-Cre mediated beta galactosidase expression in a conditional Rosa26LacZ reporter mice at embryonic day 17 [15], suggesting excision of Pten exon5 at around this developmental point.

Gene_expression (excision) of Pten

9) Confidence 0.67 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2736587 Disease Relevance 0.27 Pain Relevance 0.38

Disruption of PTEN activity in DA neurons during postmitotic developmental growth

Gene_expression (activity) of PTEN in DA neurons associated with dopamine

10) Confidence 0.67 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2736587 Disease Relevance 0.43 Pain Relevance 0.45

PTEN ablation in DA neurons (n?

Gene_expression (ablation) of PTEN in DA neurons associated with dopamine

11) Confidence 0.67 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2736587 Disease Relevance 0.16 Pain Relevance 0.29

The expression level of clonidine-induced phosphorylated PTEN (phosphatase and tensin homolog deleted on chromosome ten) was significantly increased in diabetic aortas, but chronic simvastatin did not affect it.

Gene_expression (expression) of PTEN in aortas associated with diabetes mellitus and clonidine

12) Confidence 0.62 Published 2008 Journal J. Pharmacol. Sci. Section Abstract Doc Link 18391484 Disease Relevance 0.92 Pain Relevance 0.35

In the SOL muscle, there was no effect of PTEN ablation on insulin stimulated PKB Thr308 phosphorylation (Figure S2).

Gene_expression (ablation) of PTEN in muscle

13) Confidence 0.60 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2905373 Disease Relevance 0.23 Pain Relevance 0

The MCK-Cre and PTEN flox/flox mice were mated and the subsequent offspring were then used as breeders to generate MCK-Cre controls termed PTEN+/+ (PTEN+/+ MCK-Cre+/?)

Gene_expression (/) of PTEN

14) Confidence 0.60 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2905373 Disease Relevance 0.07 Pain Relevance 0.04

The MCK-Cre and PTEN flox/flox mice were mated and the subsequent offspring were then used as breeders to generate MCK-Cre controls termed PTEN+/+ (PTEN+/+ MCK-Cre+/?)

Gene_expression (mated) of PTEN

15) Confidence 0.60 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2905373 Disease Relevance 0.13 Pain Relevance 0.04

The MCK-Cre and PTEN flox/flox mice were mated and the subsequent offspring were then used as breeders to generate MCK-Cre controls termed PTEN+/+ (PTEN+/+ MCK-Cre+/?)

Gene_expression (/) of PTEN

16) Confidence 0.60 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2905373 Disease Relevance 0.07 Pain Relevance 0.04

Therefore, while the increased activation of PKB in the overloaded PLN muscle of the PTEN?

Gene_expression (muscle) of PTEN in muscle

17) Confidence 0.60 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2905373 Disease Relevance 0.22 Pain Relevance 0

PCR products were then subjected to electrophoresis on a 2% agarose gel and genotype was established by the presence of a 500 bp band from the MCK-Cre reaction and either a 200 bp product for PTEN?

Gene_expression (product) of PTEN in band

18) Confidence 0.60 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2905373 Disease Relevance 0 Pain Relevance 0

To confirm if Pten deletion was specific to DAT expressing regions, primers specific to the recombination (delta5) were developed.

Gene_expression (deletion) of Pten

19) Confidence 0.59 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2736587 Disease Relevance 0.15 Pain Relevance 0.25

We found that Pten deletion protects DA neurons during this partial 6OHDA lesion and prevents fiber loss in the lesioned striatum when compared to control animals.

Gene_expression (deletion) of Pten in striatum associated with dopamine

20) Confidence 0.59 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2736587 Disease Relevance 0 Pain Relevance 0.58

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