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Phenotypic heterogeneity in the stargazin allelic series

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Abstract

The stargazer mutant mouse is characterized by its ataxic gait, head tossing, and absence seizures. The mutation was identified in the gamma2 subunit gene of the high voltage-dependent calcium channel, Cacng2. Subsequently, two allelic variants of stargazer have arisen, waggler and stargazer 3J. In this study, we have compared these new alleles to the original stargazer allele. All three mutations affect the Cacng2 mRNA levels as they all arise from disruptions within the introns of this gene. Our results show that the mutations cause reduced Cacng2 mRNA and protein levels. Stargazer and waggler mice have the least amount of mRNA and undetectable protein, whereas stargazer 3J appears to be the mildest allele, both in terms of the phenotype and protein expression. Electroencephalographic (EEG) analysis confirmed that stargazer has frequent spike-wave discharges (SWDs); the average duration of each discharge burst is 5 seconds and recurs every minute. The waggler allele causes a greater variation in SWD activity depending on the individual mouse, and the stargazer 3J mouse has no SWDs. The preliminary characterization of this heterogeneous allelic series provides a basis to explore more biochemical and physiological parameters relating to the role of the Cacng2 product in calcium channel activity, AMPA receptor localization, and cerebellar disturbances.

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Acknowledgements

We thank Drs. Susan Ackerman and Muriel Davisson for critical reviews of this manuscript. This work was supported by a grant from the NIH NS32801 to Verity A. Letts. Myoung-Goo. Kang was partly funded by an Epilepsy Foundation Predoctoral Fellowship, and Kevin P. Campbell is an Investigator of the Howard Hughes Medical Institute.

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Correspondence to Verity A. Letts.

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Letts, V.A., Kang, MG., Mahaffey, C.L. et al. Phenotypic heterogeneity in the stargazin allelic series . Mamm Genome 14, 506–513 (2003). https://doi.org/10.1007/s00335-003-2268-x

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  • DOI: https://doi.org/10.1007/s00335-003-2268-x

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