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Characterisation of immune cell function in fragment and full-length Huntington's disease mouse models.

Träger U, Andre R, Magnusson-Lind A, Miller JR, Connolly C, Weiss A, Grueninger S, Silajdžić E, Smith DL, Leavitt BR, Bates GP, Björkqvist M, Tabrizi SJ - Neurobiol. Dis. (2014)

Bottom Line: Inflammation is a growing area of research in neurodegeneration.However, bone marrow CD11b(+) cells did not show the same hyper-responsive phenotype as spleen and blood cells.Taken together, these results show significant promise for these mouse models to be used to study targeting innate immune pathways identified in human cells, thereby helping to understand the role the peripheral immune system plays in HD progression.

View Article: PubMed Central - PubMed

Affiliation: UCL Institute of Neurology, Dept. of Neurodegenerative Disease, London, UK.

No MeSH data available.


Related in: MedlinePlus

Mutant HTT levels in R6/2 spleen and bone marrow. Single cell suspensions obtained from bone marrow, spleen as well as magnetically sorted spleen and bone marrow CD11b+ cells from 12-week old R6/2 and wild-type mice (n = 8), were lysed and used to assess mHTT levels. TR-FRET measures demonstrated that mHTT levels are similar in CD11b+ immune cells isolated from spleen and bone morrow. No mHTT was detected in control mice (n = 3). Data shown as percentage of the signal intensities over lysis buffer background signal after normalisation to total protein levels.
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f0020: Mutant HTT levels in R6/2 spleen and bone marrow. Single cell suspensions obtained from bone marrow, spleen as well as magnetically sorted spleen and bone marrow CD11b+ cells from 12-week old R6/2 and wild-type mice (n = 8), were lysed and used to assess mHTT levels. TR-FRET measures demonstrated that mHTT levels are similar in CD11b+ immune cells isolated from spleen and bone morrow. No mHTT was detected in control mice (n = 3). Data shown as percentage of the signal intensities over lysis buffer background signal after normalisation to total protein levels.

Mentions: However, the measurement of mHTT levels showed that CD11b+ cells isolated from the bone marrow and spleen of 12-week old R6/2 mice are not significantly different (Fig. 4), suggesting that this is not the explanation for why bone marrow myeloid cells from HD mouse models are not hyper-responsive. Interestingly, whilst mHTT levels in whole spleen are similar to those in cells that have been sorted by CD11b+, unsorted bone marrow that contains a large number of stem cells shows increased levels of mHTT expression compared to sorted cells (Fig. 4).


Characterisation of immune cell function in fragment and full-length Huntington's disease mouse models.

Träger U, Andre R, Magnusson-Lind A, Miller JR, Connolly C, Weiss A, Grueninger S, Silajdžić E, Smith DL, Leavitt BR, Bates GP, Björkqvist M, Tabrizi SJ - Neurobiol. Dis. (2014)

Mutant HTT levels in R6/2 spleen and bone marrow. Single cell suspensions obtained from bone marrow, spleen as well as magnetically sorted spleen and bone marrow CD11b+ cells from 12-week old R6/2 and wild-type mice (n = 8), were lysed and used to assess mHTT levels. TR-FRET measures demonstrated that mHTT levels are similar in CD11b+ immune cells isolated from spleen and bone morrow. No mHTT was detected in control mice (n = 3). Data shown as percentage of the signal intensities over lysis buffer background signal after normalisation to total protein levels.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4262574&req=5

f0020: Mutant HTT levels in R6/2 spleen and bone marrow. Single cell suspensions obtained from bone marrow, spleen as well as magnetically sorted spleen and bone marrow CD11b+ cells from 12-week old R6/2 and wild-type mice (n = 8), were lysed and used to assess mHTT levels. TR-FRET measures demonstrated that mHTT levels are similar in CD11b+ immune cells isolated from spleen and bone morrow. No mHTT was detected in control mice (n = 3). Data shown as percentage of the signal intensities over lysis buffer background signal after normalisation to total protein levels.
Mentions: However, the measurement of mHTT levels showed that CD11b+ cells isolated from the bone marrow and spleen of 12-week old R6/2 mice are not significantly different (Fig. 4), suggesting that this is not the explanation for why bone marrow myeloid cells from HD mouse models are not hyper-responsive. Interestingly, whilst mHTT levels in whole spleen are similar to those in cells that have been sorted by CD11b+, unsorted bone marrow that contains a large number of stem cells shows increased levels of mHTT expression compared to sorted cells (Fig. 4).

Bottom Line: Inflammation is a growing area of research in neurodegeneration.However, bone marrow CD11b(+) cells did not show the same hyper-responsive phenotype as spleen and blood cells.Taken together, these results show significant promise for these mouse models to be used to study targeting innate immune pathways identified in human cells, thereby helping to understand the role the peripheral immune system plays in HD progression.

View Article: PubMed Central - PubMed

Affiliation: UCL Institute of Neurology, Dept. of Neurodegenerative Disease, London, UK.

No MeSH data available.


Related in: MedlinePlus