Background Huntington's disease (HD) causes widespread changes in CNS as well as systemic abnormalities. One of the typical HD symptoms is an innate immune activation in periphery. This phenotype can be observed many years before the predicted onset of neurological symptoms, which designates immune activation as a potential biomarker of HD progression. To carefully monitor the early HD progression, we have established a biomedical model of HD—miniature pigs transgenic for N-terminal part of human mutated huntingtin (mt htt, 548 aa, 124Q). Each litter represents wt (controls) and tg siblings in an approximate ratio 1:1.
Aims (i) characterisation of immune activation in control and htt tg minipigs; (ii) correlation of cytokine levels with the age of animals and HD symptoms.
Methods The immunological characteristics have been studied on age-matched minipigs with the same genetic background (parents, F1 and F2 generation; 22 animals in total). The levels of 10 cytokines in the blood serum were examined by targeted proteomic profiling using porcine antibody microarrays.
Results Our preliminary results indicate changes in several cytokine levels between control and transgenic animals. The cytokine profiling together with monitoring of monocyte activation and behavioural changes will longitudinally continue in 3 month intervals to follow-up the disease progression.
Conclusion Provided that the changes in our model will be in correlation with changes seen in patients, HD transgenic miniature pigs would represent a perspective and valuable large animal model for translational studies of HD biomarkers.
- Immune activation in HD
- Cytokine profiling
- Monocyte activation
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