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| 17853944 | NOX2 | NOX2 | 7.1 | dysregulated redox stress in ALS mice caused by NADPH oxidases Nox1 and Nox2 significantly influenced the progression of motor neuron disease | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | stress in ALS mice caused by NADPH oxidases Nox1 and Nox2 significantly influenced the progression of motor neuron disease caused by | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | However 50% survival rates were enhanced significantly more by Nox2 deletion than by Nox1 deletion | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | female ALS mice containing only 1 active X-linked Nox1 or Nox2 gene also had significantly delayed disease onset but showed normal | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Nox activity in spinal cords from Nox2 heterozygous female ALS mice was approximately 50% that of WT | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | ALS mice suggesting that random X-inactivation was not influenced by Nox2 gene deletion | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | that SOD1 G93A ALS transgenic mice produce elevated levels of Nox2 gp91phox and superoxide in spinal cord microglia ( 8 | |  |
| 17853944 | GP91PHOX | gp91phox | 2.0 | SOD1 G93A ALS transgenic mice produce elevated levels of Nox2 gp91phox and superoxide in spinal cord microglia ( 8 | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Seven known NADPH oxidases (Nox1, Nox1 Nox2 Nox3 Nox4 Nox5 Duox1 and Duox2 are thought to play | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Although Nox2 expression increases in microglia of the spinal cord of SOD1 | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | the spinal cord of SOD1 G93A transgenic mice deletion of Nox2 on a C57BL/6J C57BL 6J inbred background of SOD1 G93A | |  |
| 17853944 | NOX2 | NOX2 | 7.1 | Nox1 and Nox2 are closely related homologs in the Nox gene | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Nox1 and Nox2 are closely related homologs in the Nox gene family and | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | To this end we performed studies comparing the contribution of Nox2 or Nox1 deletion on disease progression in mixed hybrid SOD1 | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | disrupting either of these NADPH oxidase genes ( Nox1 or Nox2 significantly delayed the progression of motor neuron disease in a | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | mice lacking a single copy of the X-chromosomal Nox1 or Nox2 genes also exhibited significantly increased survival rates | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | of random X-inactivation a 50% reduction in Nox1 - or Nox2 -expressing cells has a substantial therapeutic benefit in ALS mice | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | (b) b Nox2 gp91phox KO mice ( 23 were also obtained from The | |  |
| 17853944 | GP91PHOX | gp91phox | 2.0 | (b) b Nox2 gp91phox KO mice ( 23 were also obtained from The Jackson | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | The generation of SOD1 G93A transgenic mice on the Nox2 -KO or Nox1 -KO backgrounds were achieved using the following | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Because both Nox2 and Nox1 genes are on the X chromosome 2 rounds | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Hemizygous SOD1 G93A transgenic males were bred to Nox2 _amp_#x02013;/_amp_#x02013; _amp_#x02013 _amp_#x02013 or Nox1 _amp_#x02013;/_amp_#x02013; _amp_#x02013 _amp_#x02013 females | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | breeding against SOD1 G93A hemizygous Nox -KO males (i.e., i.e. Nox2 +/_amp_#x02013; _amp_#x02013 _amp_#x000d7 SOD1 G93A / Nox2 _amp_#x02013;/Y _amp_#x02013 Y | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | males (i.e., i.e. Nox2 +/_amp_#x02013; _amp_#x02013 _amp_#x000d7 SOD1 G93A / Nox2 _amp_#x02013;/Y _amp_#x02013 Y or Nox1 +/_amp_#x02013; _amp_#x02013 _amp_#x000d7 SOD1 G93A | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | bred against SOD1 G93A hemizygous Nox -WT males (i.e., i.e. Nox2 +/_amp_#x02013; _amp_#x02013 _amp_#x000d7 SOD1 G93A / Nox2 +/Y Y or | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | males (i.e., i.e. Nox2 +/_amp_#x02013; _amp_#x02013 _amp_#x000d7 SOD1 G93A / Nox2 +/Y Y or Nox1 +/_amp_#x02013; _amp_#x02013 _amp_#x000d7 SOD1 G93A / | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Genotyping for Nox2 and SOD1 G93A mice was performed by standard PCR protocols | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | and the mouse IL2 CT for all mice in the Nox2 F2 generation | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | the study because their presymptomatic weight exceeded 40 g 2 Nox2 -WT 1 Nox2 -HET and 1 Nox2 -KO | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | their presymptomatic weight exceeded 40 g 2 Nox2 -WT 1 Nox2 -HET and 1 Nox2 -KO | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | 40 g 2 Nox2 -WT 1 Nox2 -HET and 1 Nox2 -KO | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Nox2 -KO mice also hemizygous for the SOD1 G93A transgene were | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | did not alter the course of disease SOD1 G93A / Nox2 -WT mice were put on antibiotic water at 90 days | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Eye infection in Nox2 -HET females hemizygous for the SOD1 G93A transgene was only | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | of the 8 females analyzed and was never observed in Nox2 -KO mice lacking the SOD1 G93A transgene | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | lysates made from the lumbar region of 120-day-old SOD1 G93A Nox2 -WT SOD1 G93A Nox2 -KO and nontransgenic mice | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | lumbar region of 120-day-old SOD1 G93A Nox2 -WT SOD1 G93A Nox2 -KO and nontransgenic mice | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Results and Discussion Gene deletion of Nox1 or Nox2 increases survival and slows disease progression in SOD1 G93A transgenic | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | We bred female Nox1 -KO and Nox2 -KO mice to hemizygous male SOD1 G93A ALS mice (Supplemental | |  |
| 17853944 | NOX2 | NOX2 | 7.1 | possible genotypes in both male and female siblings because both Nox1 and Nox2 are on the X chromosome | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | in both male and female siblings because both Nox1 and Nox2 are on the X chromosome | |  |
| 17853944 | NOX2 | NOX2 | 7.1 | The Nox1 and Nox2 mice were both maintained on the C57BL/6 C57BL | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | The Nox1 and Nox2 mice were both maintained on the C57BL/6 C57BL 6 background | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | maintained on the C57BL/6 C57BL 6 background however only the Nox2 mice were inbred to greater than 13 generations ( Nox1 | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Unlike a previous study evaluating deletion of the Nox2 gene in SOD1 G93A C57BL/6J C57BL 6J inbred transgenic mice | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Homozygous deletion of either Nox1 or Nox2 significantly delayed the death of hemizygous SOD1 G93A ALS mice | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Nox2 gene deletion had the greatest impact on survival in both | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | impact on survival in both male and female mice ( Nox2 -WT 132 days Nox2 -KO 229 days and also led | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | both male and female mice ( Nox2 -WT 132 days Nox2 -KO 229 days and also led to a 4-fold increase | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | The finding of an increased survival index in Nox2 -KO SOD1 G93A transgenic mice is significant because to our | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Given the significant 97-day increase in survival of Nox2 -KO SOD1 G93A B6SJL mice in our study compared with | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | with the 13-day increase observed in a previous study using Nox2 -KO SOD1 G93A congenic C57BL/6J C57BL 6J mice ( 8 | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | congenic C57BL/6J C57BL 6J mice ( 8 we investigated the Nox2 dependence of several disease-associated phenotypes at the cellular level | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Enhanced survival of ALS Nox2 -KO mice correlated with higher motor neuron counts in the | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Deletion of Nox2 also resulted in reduced redox stress in spinal cords of | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | These findings were similar to those observed in the previous Nox2 -KO SOD1 G93A congenic C57BL/6J C57BL 6J study ( 8 | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | death (Figure Figure 1 D were both significantly reduced in Nox2 -KO SOD1 G93A mice compared with Nox2 -WT SOD1 G93A | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | significantly reduced in Nox2 -KO SOD1 G93A mice compared with Nox2 -WT SOD1 G93A mice | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | finding of decreased motor neuron disease in male and female Nox2 -KO ALS mice (Figure Figure 3 B_amp_#x02013 D | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | To determine whether Nox2 deficiency protected SOD1 G93A mice from muscle atrophy the weight | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | At 100 days Nox2 -KO SOD1 G93A mice demonstrated significant protection from loss in | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | significant protection from loss in hind-limb muscle mass compared with Nox2 -WT SOD1 G93A mice (Supplemental Supplemental Figure 5 A and | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | These differences in muscle mass between the Nox2 genotypes of SOD1 G93A mice correlated with changes in muscle | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Furthermore Nox2 -KO SOD1 G93A mice were indistinguishable from nontransgenic littermates for | |  |
| 17853944 | NOX2 | NOX2 | 7.1 | seen in our studies (129 129 and 132 days for Nox1 and Nox2 backgrounds respectively were very similar to SOD1 G93A | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | our studies (129 129 and 132 days for Nox1 and Nox2 backgrounds respectively were very similar to SOD1 G93A B6SJL hybrid | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Because a previous study using inbred C57BL/6 C57BL 6 Nox2 -KO SOD1 G93A mice demonstrated much smaller increases in survival | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | in survival ( 8 compared with our mixed B6SJL background Nox2 -KO SOD1 G93A mice we hypothesize that multiple SJL-derived modifier | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | that multiple SJL-derived modifier genes likely act in concert with Nox2 deficiency to significantly enhance survival of SOD1 G93A mice | |  |
| 17853944 | NOX2 | NOX2 | 7.1 | degree of variability in survival among siblings for the various Nox1 and Nox2 SOD1 G93A genotypes in the F1 and F2 | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | variability in survival among siblings for the various Nox1 and Nox2 SOD1 G93A genotypes in the F1 and F2 generations (Supplemental | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | An embryonic stem cell_amp_#x02013 derived 129 segment linked to the Nox2 gene deletion near the telomere of the X chromosome likely | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | the telomere of the X chromosome likely segregates with the Nox2 mutant allele | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | to account for the increased survival seen in the B6SJL Nox2 -KO SOD1 G93A mice for 2 reasons | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Second this 129-derived segment linked to the targeted Nox2 allele on the telomere of the X chromosome would certainly | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | in the previous study that used inbred C57BL/6 C57BL 6 Nox2 -KO SOD1 G93A mice ( 8 | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Because we used the same inbred C57BL/6 C57BL 6 Nox2 -KO mice for breeding yet observed widely divergent survival rates | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | mice for breeding yet observed widely divergent survival rates of Nox2 -KO SOD1 G93A mice it is unlikely this 129-linked segment | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Interestingly Nox2 -HET female ALS mice also demonstrated significant increases in survival | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | female ALS mice also demonstrated significant increases in survival ( Nox2 -WT 132 days Nox2 -HET 186 days Figure 1 A | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | demonstrated significant increases in survival ( Nox2 -WT 132 days Nox2 -HET 186 days Figure 1 A and Figure 3 A | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | substantiated the finding of decreased motor neuron disease in female Nox2 -HET ALS mice (Figure Figure 3 B_amp_#x02013 D | |  |
| 17853944 | NOX2 | NOX2 | 7.1 | Both Nox1 and Nox2 genes reside on the X chromosome | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Both Nox1 and Nox2 genes reside on the X chromosome | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | in female patients with X-linked chronic granulomatous disease caused by Nox2 gene mutations ( 17 | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Given the significant protective effect seen in Nox2 -HET female mice we sought to determine how dosage of | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | -HET female mice we sought to determine how dosage of Nox2 activity in the spinal cord might influence disease progression in | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | end-stage disease Nox activity in the spinal cords of female Nox2 -HET SOD1 G93A mice fell between that of female Nox2 | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Nox2 -HET SOD1 G93A mice fell between that of female Nox2 -KO and Nox2 -WT SOD1 G93A mice (Figure Figure 1 | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | G93A mice fell between that of female Nox2 -KO and Nox2 -WT SOD1 G93A mice (Figure Figure 1 C | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | This suggests that X-inactivation likely occurs randomly in female Nox2 -HET SOD1 G93A mice with about 50% of the microglia | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | microglia and neuronal cell types predicted to be deficient for Nox2 function | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | These findings demonstrate that a 50% reduction of Nox2 activity in the spinal cord has a significant impact on | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | It is presently unclear why chimerism for Nox2 expression in the spinal cord significantly influences survival but not | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Given that Nox2 is highly expressed in microglia of SOD1 G93A transgenic mice | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | microglia of SOD1 G93A transgenic mice ( 8 chimerism of Nox2 gene expression in microglia appears to influence disease progression | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | demonstrating significantly enhanced survival in female ALS mice with chimeric Nox2 expression suggest that SOD1 G93A expression in microglia may directly | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | expression in microglia may directly influence deleterious cell-autonomous function of Nox2 | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Results and Discussion Nox2 deficiency leads to an enhanced predisposition to lethal eye infections | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Notably in the Nox2 -KO SOD1 G93A transgenic background we observed a high frequency | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | These infections were never observed in Nox2 -KO littermates lacking the SOD1 G93A transgene | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Importantly antibiotic treatment of control ALS mice on the WT Nox2 background did not alter either the progression of motor neuron | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | was rapid accumulation of secretions around the eye from affected Nox2 -KO SOD1 G93A transgenic mice suffering from infections (Supplemental Supplemental | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | glands (the the Harderian gland and lacrimal gland of affected Nox2 -KO SOD1 G93A transgenic mice compared with Nox2 -WT SOD1 | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | of affected Nox2 -KO SOD1 G93A transgenic mice compared with Nox2 -WT SOD1 G93A transgenic mice ( n = 3 per | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | First the Harderian gland of Nox2 -WT SOD1 G93A transgenic mice always contained accumulated porphyrin aggregates | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | lumen of glandular tubules that were never seen in affected Nox2 -KO SOD1 G93A transgenic mice (Supplemental Supplemental Figure 6 C | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | possible that altered secretions from the Harderian gland of affected Nox2 -KO SOD1 G93A transgenic mice influence the observed increased predisposition | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | architecture of the lacrimal glands were also observed in affected Nox2 -KO SOD1 G93A transgenic mice (Supplemental Supplemental Figure 6 D | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | may account for increased incidence of infection in eyes of Nox2 -KO SOD1 G93A transgenic mice | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | overexpression of SOD1 G93A manifests these abnormalities only on the Nox2 -KO background | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | the findings imply potential new functions for both SOD1 and Nox2 in eye innate immunity | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Compromised immune function in Nox2 -KO animals likely contributed to the lack of inflammation in | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | explain why the infection was only present in the ALS Nox2 -KO mice | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | microglia during the progression of ALS disease and that in Nox2 -KO mice there is a marked decrease in the number | |  |
| 17853944 | NOX2 | NOX2 | 7.1 | survival and delayed disease onset when 2 related Nox genes Nox1 and Nox2 were deleted | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | delayed disease onset when 2 related Nox genes Nox1 and Nox2 were deleted | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | findings in female SOD1 G93A transgenic mice heterozygous for the Nox2 X-linked gene and hence containing 50% Nox2-inactive cells suggest that | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | failed to find substantial protection against motor neuron defects in Nox2 -KO SOD1 G93A transgenic mice | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | life span seen in the Nox1 -KO compared with the Nox2 -KO ALS mice would suggest that modifier genes must act | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | would suggest that modifier genes must act in concert with Nox2 deficiency to provide substantial improvements in survival | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | The potential existence of additional modifier genes that may influence Nox2 function in ALS would be particularly relevant to human ALS | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | reported as a consequence of disrupting a single gene ( Nox2 | |  |
| 17853944 | NOX2 | NOX2 | 7.1 | studies also demonstrate that more than 1 Nox gene ( Nox1 and Nox2 can influence disease progression in ALS mice | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | demonstrate that more than 1 Nox gene ( Nox1 and Nox2 can influence disease progression in ALS mice | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | in female ALS mice suggest that a 50% reduction in Nox2 activity can significantly alter the progression of disease in this | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Figure 1 Deletion of NADPH oxidase genes ( Nox1 or Nox2 enhances survival and survival index in ALS mice and significantly | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Figure 2 Nox2 deficiency rescues motor neuron death in the spinal cords of | |  |
| 17853944 | NOX2 | Nox2 | 7.1 | Figure 3 Disease phenotyping of Nox2 genotypes on the SOD1 G93A ALS background | |  |
| 18598679 | NOX2 | Nox2 | 2.5 | Wu et al. 2006 and deletion of either Nox1 or Nox2 gene significantly slowed disease progression and improved survival of ALS | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | transgenic sod1 g93a mice [c57bl/6j tgn sod1 g93a 1gur dl ] were crossed with gp91 phox deficient mice b6.129s6 cybb tm1din . | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | primer sequences for gp91 phox glial fibrillary acidic protein macrophage antigen complex 1 and gapdh and pcr conditions are presented in supporting text . | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | expression of nadph oxidase in the spinal cord which carries the brunt of the pathology in this als model was determined by analyzing its catalytic subunit gp91 phox . | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | both gp91 phox message and protein contents in whole tissue extracts of spinal cord rose over time in transgenic sod1 g93a mice fig 1 a b d and e in concert with the development of a glial response fig 6 which is p | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | histological evaluation of the spinal cord of symptomatic transgenic sod1 g93a mice showed numerous gp91 phox positive cells primarily in the gray matter of the anterior horn fig 1 g whereas sparse staining was observed in the spinal cord of age matched nontransgenic controls fig 1 f . | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | consistent with nadph oxidase expression by professional phagocytes confocal microscopy demonstrated the colocalization of the gp91 phox subunit with a microglial marker the ricinus communis agglutinin lectin fig 1 h _amp_#x02013; j ; no gp91 phox colocalization was detected with the motor neuron marker nonphosphorylated neurofilament | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | subunit with a microglial marker the ricinus communis agglutinin lectin fig 1 h _amp_#x02013; j ; no gp91 phox colocalization was detected with the motor neuron marker nonphosphorylated neurofilament heavy chain or with the astrocyte marker glial fibrillary acid protein data not shown . | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | in contrast in symptomatic transgenic sod1 g93a mice carrying the wild type gp91 phox allele sod g93a /gp91 phox+ spinal cord ethidium fluorescence was intense fig 1 l and coincided anatomically with the areas of gp91 phox expression fig 1 g and microglial activation fig 6 . | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | + spinal cord ethidium fluorescence was intense fig 1 l and coincided anatomically with the areas of gp91 phox expression fig 1 g and microglial activation fig 6 . | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | symptomatic transgenic sod1 g93a /gp91 phox+ mice but not age matched sod1 g93a /gp91 phox_amp_#x02212; mice had increased levels of spinal cord protein carbonyl adducts compared with nontransgenic controls expressing either wild type or null | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | but not age matched sod1 g93a /gp91 phox_amp_#x02212; mice had increased levels of spinal cord protein carbonyl adducts compared with nontransgenic controls expressing either wild type or null mutant gp91 phox fig 1 n . | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | immunohistochemically the most robust labeling for protein carbonyl adducts occurred in spinal cord sections from sod1 g93a /gp91 phox+ mice at the level of cells with mixed morphology including large motor neurons fig 1 o _amp_#x02013; q . | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | consistent with the mouse data gp91 phox content was low fig 2 a and b and its immunoreactivity was faint in control postmortem spinal cords fig 2 d whereas gp91 phox content was _amp_#x02248;3 fold higher and its immunoreactivity robust in sporadic als spinal cords fig 2 e . | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | in the latter gp91 phox positive cells colocalized with the microglial associated antigen cd68 fig 2 f and were identified in all of the typical als loci of neurodegeneration including the anterior horn and the lateral cort | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | deletion of gp91 phox mitigates the disease phenotype in transgenic sod1 g93a mice. | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | transgenic sod1 g93a /gp91 phox_amp_#x02212; mice reached end stage paralysis defined as a loss of the righting reflex later than their transgenic sod1 g93a /gp91 phox+ counterparts fig 3 a which resulted in a longer lifespan of transgenic sod1 g93a /gp91 phox_amp_#x02212; mice log rank test = 15.3; p _amp_#x0003c; 0.001 . | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | compared with end stage transgenic sod1 g93a /gp91 phox+ mice age matched transgenic sod1 g93a /gp91 phox_amp_#x02212; mice had _amp_#x02248;50% more anterior horn motor neurons in the spinal cord fig 3 b _amp_#x02013; e and myelinated axons in the fifth | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | spinal cord microgliosis evidenced by macrophage antigen complex 1 immunostaining and levels of the glial cytokine il 1_amp_#x003b2; did not differ between age matched transgenic sod1 g93a /gp91 phox+ mice and sod1 g93a /gp91 phox_amp_#x02212; mice fig 7 which is published as supporting information on the pnas web site . | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | also not affected by the deficit of gp91 phox were the levels of human sod1 in transgenic sod1 g93a mice fig 7 or the size of muscle fibers in the fibularis and peroneus longus muscles in nontransgenic mice fig 3 t . | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | however protein carbonyl adducts were evident in the _amp_#x003b1; chain of the igf1 tyrosine kinase cognate receptor in the spinal cord of symptomatic transgenic sod1 g93a /gp91 phox+ mice fig 4 a and b ; similar results were obtained for the _amp_#x003b2; chain of igf1 receptor data not shown . | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | however there were fewer phospho igf1 receptor immunoreactive cells in spinal cord sections from symptomatic transgenic sod1 g93a /gp91 phox+ mice than from age matched sod1 g93a /gp91 phox_amp_#x02212; mice fig 4 c _amp_#x02013; e . | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | as fewer cells that were immunoreactive for a downstream target of akt phospho bad fig 4 h _amp_#x02013; j and smaller phospho bad:total bad ratios fig 4 k and l in symptomatic transgenic sod1 g93a /gp91 phox+ mice compared with their age matched sod1 g93a /gp91 phox_amp_#x02212; counterparts. | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | these data further support the idea that oxidative modification of igf1 receptor in symptomatic transgenic sod1 g93a /gp91 phox+ mice is associated with a range of molecular perturbations. | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | germane to the molecular basis of this deleterious effect on motor neurons is our finding that virtually all spinal cord microglial cells express the gp91 phox subunit of the oxidant producing enzyme nadph oxidase fig 1 . | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | agreeing with the fact that in nonactivated phagocytes nadph oxidase is quiescent 7 gp91 phox positive cells in spinal cords from 1 to 4 month old nontransgenic mice had a morphology of resting microglia and did not seem to produce ros figs 1 and 6 . | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | our results also show that abrogation of the gp91 phox subunit of nadph oxidase in transgenic sod1 g93a mice eliminates the production of microglial derived ros fig 1 m and importantly prolongs survival and retards neurodegeneration in this als model fig | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | deletion of gp91 phox in transgenic sod1 g93a mice did not alter the spinal cord microglial response or the expression of human sod1 in transgenic sod1 g93a mice fig 7 which is a known determinant of disease severity in t | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | however the magnitude of benefit afforded by gp91 phox deletion in transgenic sod1 g93a mice argues that targeting neuroinflammation by inhibiting just one of its mediators such as nadph oxidase may not be sufficient to produce robust and lasting neuropr | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | nevertheless whether transgenic sod1 g93a mice carrying the gp91 phox null mutation reach end stage paralysis later and exhibit an attenuated neurodegenerative process because of some effects at the skeletal muscle level is an interesting possibility that cannot be exc | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | a _amp_#x02013; e spinal cord gp91 phox mrna a and d and protein b and e in 1 month old asymptomatic to 4 month old end stage transgenic sod1 more ... | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | a and b immunoblots and bar graph for gp91 phox using spinal cord extracts from six normal controls and six age matched als patients. | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | deletion of gp91 phox increases lifespan and lessens neurodegeneration in transgenic sod1 g93a mice. | |  |
| 16877542 | gp91 phox | gp91 phox | 1.0 | a survival comparison of transgenic sod1 g93a /gp91 phox+ mice red 122.0 _amp_#x000b1; 1.7 days; n = 19 and transgenic sod1 g93a /gp91 phox_amp_#x02212; littermates more ... | |  |
| 18598679 | gp91 phox | gp91 phox | 1.0 | nadph oxidase subunits gp91 phox p47 phox and il 1_amp_#x3b2; mrna expression were evaluated by semiquantitative rt pcr using gapdh gene as internal standard. | |  |
| 18598679 | gp91 phox | gp91 phox | 1.0 | fig. 5._amp_#xa0;changes in the message level of il 1_amp_#x3b2; gp91 phox and p47 phox in slice cultures after lps exposure. | |  |
| 18598679 | gp91 phox | gp91 phox | 1.0 | c representative bands of nadph oxidase subunits gp91 phox and p47 phox mrna expression in slices treated with medium alone or 30_amp_#xa0;_amp_#x3bc;g/ml lps for 2_amp_#xa0;weeks after 1_amp_#xa0;week in culture. | |  |
| 18598679 | gp91 phox | gp91 phox | 1.0 | d ratio of pcr product from gp91 phox and p47 phox to that of gapdh mrna. | |  |
| 18598679 | gp91 phox | gp91 phox | 1.0 | we also investigated the message levels of nadph oxidase subunits gp91 phox and p47 phox . | |  |
| 18598679 | gp91 phox | gp91 phox | 1.0 | the mrna expression of gp91 phox in the slices treated with lps significantly increased compared to the controls figs 5 c and d . | |  |
| 18598679 | gp91 phox | gp91 phox | 1.0 | nadph oxidase also known as phagocytic oxidase phox is a dormant enzyme in resting cells composed of two membrane bound components gp91 phox and p22 phox and several cytosolic components including p47 phox p40 phox p67 phox and rac1/2 babior et al. 2002 . | |  |
| 18598679 | gp91 phox | gp91 phox | 1.0 | gp91 phox is the catalytic core of the enzyme. | |  |
| 18598679 | gp91 phox | gp91 phox | 1.0 | in the present study we found that nadph oxidase was activated as indicated by the up regulation of membranous subunit gp91 phox mrna expression and the translocation of cytosolic component p47 phox to the membrane following lps challenge. | |  |