T-type Ca2+ channels have been implicated in tremorogenesis and motor coordination. The alpha 1 subunit of the Ca(v)3.1 T-type Ca2+ channel is highly expressed in motor pathways in the brain, but knockout of the Ca(v)3.1 gene (alpha(-/-)(1G)) per se causes no motor defects in mice. Thus, the role of Ca(v)3.1 channels in motor control remains obscure in vivo. Here, we investigated the effect of the Ca(v)3.1 knockout in the null genetic background of alpha 1 GABA(A) receptor (alpha 1(-/-)) by generating the double mutants (alpha 1(-/-)/alpha(-/-)(1G)). alpha 1(-/-)/alpha(-/-)(1G) mice showed severer motor abnormalities than alpha 1(-/-) mice as measured by potentiated tremor activities at 20 Hz and impaired motor learning. Propranolol, an anti-ET drug that is known to reduce the pathologic tremor in alpha 1(-/-) mice, was not effective for suppressing the potentiated tremor in alpha 1(-/-)/alpha(-/-)(1G) mice. In addition, alpha 1(-/-)/alpha(-/-)(1G) mice showed an age-dependent loss of cerebellar Purkinje neurons. These results suggest that alpha 1(-/-)/alpha(-/-)(1G) mice are a novel mouse model for a distinct subtype of ET in human and that Ca(v)3.1 T-type Ca2+ channels play a role in motor coordination under pathological conditions. (C) 2011 Elsevier Inc. All rights reserved.