Leaner mouse

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. 

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...

Lorenzon NM, Lutz CM, Frankel WN, Beam KG (1998) Altered calcium channel currents in Purkinje cells of the neurological mutant mouse leaner. J Neurosci 18 4482-4489. 

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. 

Herlitze S, Garcia DE, Mackie K, Hille B, Scheuer T, Catterall WA (1996) Modulation of Ca2+ channels by G-protein beta gamma subunits. Nature 380 258-62 Herrup K, Wilczynski SL (1982) Cerebellar cell degeneration in the leaner mutant mouse. Neuroscience 7 2185-96... 

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... 

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