Regular ArticleGenetic and Physical Maps of the Stargazer Locus on Mouse Chromosome 15☆
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AMPA Receptors as Therapeutic Targets for Neurological Disorders
2016, Advances in Protein Chemistry and Structural BiologyCitation Excerpt :The transmembrane AMPA receptor regulatory proteins (TARPs) provide the intermolecular link between surface AMPA receptors and intracellular PDZ containing proteins such as PSD95 (Chen et al., 2000). The most well-known TARP protein, Stargazin (also known as γ-2) is the first member of the Type 1 family of TARP proteins (Tomita et al., 2003), and was identified as the mutant protein in the epileptic Stargazer mouse (Letts et al., 1997, 1998). Stargazin is widely expressed throughout the brain, particularly in the cerebellum, cerebral cortex, and hippocampus (Tomita et al., 2003), and is enriched in the PSD fraction of excitatory synapses where it is strongly associated with the AMPA receptor (Fukata et al., 2005; Tomita, Fukata, Nicoll, & Bredt, 2004; Tomita et al., 2003).
The Expanding Social Network of Ionotropic Glutamate Receptors: TARPs and Other Transmembrane Auxiliary Subunits
2011, NeuronCitation Excerpt :The first bona fide transmembrane auxiliary subunit of an iGluR was discovered through the characterization of stargazer, a spontaneous mutation in an inbred mouse line, originally distinguished by its striking behavioral phenotype—dyskinesia, severe ataxia, characteristic head-tossing, and frequent spike-wave discharges (SWDs), reminiscent of absence epilepsy in humans (Noebels et al., 1990). Genetic mapping revealed that the stargazer mutation is attributable to a single recessive mutation on mouse chromosome 15 (Letts et al., 1997). Subsequent positional cloning showed that the locus of the mutation encodes stargazin—a novel, brain-specific, low-molecular weight, tetraspanning membrane protein with homology to the voltage-gated calcium channel (VGCC) subunit γ-1, hence its alternative name, γ-2 (Letts et al., 1998) (Figure 2).
Loss of calcium channels in the cerebellum of the ataxic and epileptic stargazer mutant mouse
2009, Brain ResearchCitation Excerpt :Stargazer mice also have “spike-wave” seizures characteristic of absence epilepsy, with accompanying defects in the cerebellum and inner ear (Letts et al., 1998). The stargazers ataxic gait and frequent spike-wave discharges were linked to a single, recessive mutation on mouse chromosome 15 (Noebels et al., 1990; Letts et al., 1997), a transposon insertion in the second intron of the Cacng2 locus that silences the expression of a voltage-dependent calcium channel (VDCC) auxiliary subunit γ2, termed stargazin (Letts et al., 1998; 2003; Sharp et al., 2001). Stargazin is the only calcium channel γ-subunit expressed significantly in the cerebellum (Klugbauer et al., 2000; Fukaya et al., 2005) where it is predominantly located in Purkinje cells (PC) and granule cells (GC).
Redundancy of Ca<inf>v</inf>2.1 channel accessory subunits in transmitter release at the mouse neuromuscular junction
2007, Brain ResearchCitation Excerpt :Mice were genotyped by PCR using genomic DNA extracted from tail biopsies. Genotyping was performed as described earlier (Burgess et al., 1997; Letts et al., 1997). Stargazer and lethargic mutant mice had a reduced body weight (of ∼ 20 and 50%, respectively), compared to wild-type.
Convulsive Disorders
2007, The Mouse in Biomedical ResearchConvulsive Disorders
2007, The Mouse in Biomedical Research: History, Wild Mice, and Genetics: Volume 1-4, Second Edition
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V. E. AndersonW. A. HauserI. E. LeppikJ. L. NoebelsS. S. Rich, Eds.
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