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Disease models

Modeling effects of mutant huntingtin (HTT)-associated pathology with a conditional transgenic mouse model

Understanding how mutant HTT expression in different cell populations affects Huntington's disease (HD) pathology could provide new therapeutic insights on how to treat HD. In a conditional transgenic mouse model of HD, selectively decreasing mutant Htt expression in cortical neurons led to less severe HD-associated motor and behavioral deficits compared with baseline but did not attenuate neurodegeneration. In the mouse model, decreasing mutant Htt expression in both cortical and striatal neurons resulted in less neurodegeneration and less severe HD-associated motor and behavioral deficits compared with baseline. Next steps include studying cell-autonomous mechanisms of mutant HTT toxicities in the cortical and striatal neuronal cell types and elucidating the molecular basis of non-cell-autonomous interactions between the two neurons that result in toxicity.

SciBX 7(21); doi:10.1038/scibx.2014.623
Published online May 29, 2014

Model unpatented; licensed to CHDI Foundation Inc. and several undisclosed companies

Wang, N. et al. Nat. Med.; published online April 28, 2014;
doi:10.1038/nm.3514
Contact: X. William Yang, University of California,
Los Angeles, Calif.
e-mail:
xwyang@mednet.ucla.edu