Tottering mouse

Figure 2. Mutations in the human Cav2.1 (P/Q-type) voltage-gated calcium channel associated with Episodic Ataxia Type-2 (EA2) mutations in the Cav2.1 mouse homolog associated with tottering (tg), leaner (tgla), rolling nagoya (tgrol) and rocker phenotypes...

Zhou YD, Turner TJ, Dunlap K (2003) Enhanced G protein-dependent modulation of excitatory synaptic transmission in the cerebellum of the Ca2+ channel-mutant mouse, tottering. J Physiol 547 497—507. 

There are also a number of murine models of P/Q-type channelopathies. Leaner, Tottering, rolling Nagoya, and Rocker mice all carry mutations in the Cav2.1 calcium channel ai subunit that result in either the substitution of individual amino acids or premature truncations of the channel protein. These mice tend to show an ataxic phenotype and, in some cases, absence seizures (Lorenzon et al. 1998 Mori et al. 2000 Noebels and Sidman 1979 Zwingman et al. 2001). In addition, several of these mutations cause cerebellar atrophy (Herrup and Wilczynski 1982). When introduced into recombinant channels, these mutations tend to reduce channel activity which is consistent with reduced P/Q-type currents in neurons isolated from these mouse lines. 

Newton PM, Orr CJ, Wallace MJ, Kim C, Shin HS, Messing RO (2004) Deletion of N-type calcium channels alters ethanol reward and reduces ethanol consumption in mice. J Neurosci 24 9862-9 Noebels JL, Sidman RL (1979) Inherited epilepsy spike-wave and focal motor seizures in the mutant mouse tottering. Science 204 1334-6... 

Kilboum MR, Sherman P, Abbott LC (1998) Reduced MPTP neurotoxicity in striatum of the mutant mouse tottering. Synapse 30 205-210. 

Of note, mutations in genes encoding Ca channel subunits have been identified in a number of recessive mouse mutants with ataxia. Homozygous point mutation in the alA gene (PI 8021., domain 11 P-region) causes epilepsy and ataxia in the mutant mouse tottering (/g) (reviewed in Jen Ptacek 2000). Novel sequences in the intracellular C-terminus of the al A subunit also resulted in a mutant mouse phenotype, leaner with ataxia and epilepsy (reviewed in... 

Austin MC, Schultzberg M, Abbott LC, Montpied P, Evers JR, Paul SM, Crawley JN (1992) Expression of tyrosine hydroxylase in cerebellar Purkinje neurons of the mutant tottering and leaner mouse. Molec. Brain Res., 15, 227-240. 

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