We present here the first comprehensive behavioral analysis of the effects of a conditional knock - down (starting at 4.5 weeks of age) of WT
endogenous htt in adult mice in the absence of any potential mutant gain - of - function.
Knocking down
the endogenous htt protein resulted in significant decrease in body weight and hyperactive behavior in the open field.
While Htt null KO mice do not survive to birth (Duyao et al., 1995; Nasir et al., 1995; Zeitlin et al., 1995), mice expressing a 50 % reduction of
endogenous htt levels reveal cognitive and motor deficits (Nasir et al., 1995) and significant decreases in the number of neurons in globus pallidus and subthalamic nucleus (O'Kusky et al., 1999).
Not exact matches
Reduction of
endogenous striatal
htt using siRNA in rats expressing
Htt171 - 82Q had no further detrimental effect on neuronal survival nor
htt inclusion load indicating that partial inactivation of
endogenous WT
htt in the adult striatum (~ 50 %) had no major impact on the course of HD pathology (Drouet et al, 2009).
Reduction of
htt to 50 %
endogenous levels produces viable mice with no overt phenotypes (Duyao et al., 1995; Zeitlin et al., 1995) however more detailed evaluation has revealed deficits in cognition and motor behavior (Nasir et al., 1995) raising the possibility that lowered
htt starting in development may have adverse effects in the mouse.