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"Gene-on"

"Gene-on"

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FIGURE 6.16 Effect of inhibiting the expression of the polyQ-htt gene on the clasping behavior of HD94 mice at 18 and 34 weeks. In the "gene-off" experiment, 2 mg/ml doxycycline was given for 16 weeks in a 5% sucrose solution that was provided to the mice to drink. Both clasping score and duration in the tail suspension test was significantly increased in controls (left) from 18-34 weeks, but significantly decreased in the gene-off group. Asterisk indicates statistical significance. Reproduced with permission from Yamamoto et al., Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease. Cell 101:57-66. Copyright 2000, Elsevier.

"Gene-off"

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FIGURE 6.16 Effect of inhibiting the expression of the polyQ-htt gene on the clasping behavior of HD94 mice at 18 and 34 weeks. In the "gene-off" experiment, 2 mg/ml doxycycline was given for 16 weeks in a 5% sucrose solution that was provided to the mice to drink. Both clasping score and duration in the tail suspension test was significantly increased in controls (left) from 18-34 weeks, but significantly decreased in the gene-off group. Asterisk indicates statistical significance. Reproduced with permission from Yamamoto et al., Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease. Cell 101:57-66. Copyright 2000, Elsevier.

Huntington's model (van Dellen et al., 2000). Loss of motor coordination, clasping of limbs, and onset of seizures were all significantly delayed. Striatal volume was 13% larger in the enriched HD mice than the nonenriched mice. These improvements were not accompanied, however, by reductions in protein aggregates in striatal cells, suggesting that the effect of enrichment may be to overcome deficiencies in synaptic plasticity.

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