Thursday, May 29, 2014
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Modeling effects of mutant huntingtin
pathology with a conditional transgenic mouse model
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.
Published online May 29, 2014
Model unpatented; licensed
to CHDI Foundation Inc. and several
Wang, N. et al. Nat.
Med.; published online April 28, 2014;
Contact: X. William Yang, University of California,
Los Angeles, Calif.
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