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- W2474081356 abstract "<h3>Background</h3> Huntington9s disease (HD) is a fatal dominantly inherited neurodegenerative disease caused by the expansion of the polyCAG stretch in the gene coding ubiquitous huntingtin protein (htt). Many different HD rodent models have been generated to date. However, these are insufficient for conversion of basic research to the human clinic with regard to the increasingly restricted research on primates. One suitable and public acceptable candidate would be the pig. <h3>Aims</h3> Transgenic models vary in the extent of gene expression, brain regions involved, neuropathology and behaviours. We therefore decided to develop a rapid onset minipig model of HD in which timed neuropathology and motor impairments would be predictable, robust and experimentally testable. <h3>Methods</h3> The right striata of normal 4-month-old minipigs received multiple injections of LVs (HIV1-HD-548aa-145Q or 23Q) in order to infect the entire volume of the striatum by using a special pig head holder (Neurologic) coupled with motorised stereotactic and microinjection apparatus controlled by PC (Stoelting and Neurostar). <h3>Results</h3> Immunoperoxidase labelling with 1C2 revealed intense mutant htt immunoreactivity in neurons within the striatum ipsilateral to the injection as early as 4 weeks after injection in 145Q injected minipigs. At this time, some mEM48 labelled neurons with aggregates appeared in the striatum. Intense mEM48 labelling of degenerating neurons with aggregates in the nucleus, cell body and processes was detected in the 145Q injected minipigs 3 months after LVs injection. <h3>Conclusion</h3> We have shown that the human mutant htt induced formation of aggregates in the neuronal nuclei, cell body and processes in miniature pig. However, the spread of LVs was not satisfactory (∼200 μm from the injection site). We therefore recently injected young minipigs (7 weeks old) with several (3–8) injections of AAV and LVs with total volume of 10–25 μl per injection in order to get the widest spread and to evoke HD phenotype." @default.
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- W2474081356 date "2010-09-01" @default.
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- W2474081356 title "A27 Expression of the human mutant huntingtin in minipig striatum induced formation of EM48+ inclusions in the neuronal nuclei, cytoplasm and processes" @default.
- W2474081356 doi "https://doi.org/10.1136/jnnp.2010.222570.27" @default.
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