Cacna1a^tg
Spontaneous Allele Detail

Summary

• Symbol: Cacna1a^tg
• Name: calcium channel, voltage-dependent, P/Q type, alpha 1A subunit; tottering
• MGI ID: MGI:1856209
• Synonyms: alpha1A^tg, tg
• Gene: Cacna1a Location: Chr8:85065268-85366875 bp, + strand Genetic Position: Chr8, 40.95 cM
• Alliance: Cacna1a^tg page

Mutation origin

• Strain of Origin: DBA/2J

Mutation description

• Allele Type: Spontaneous (Not Specified)
• Mutation: Single point mutation
• Mutation details: A C to T point mutation results in a replacement of proline with leucine at position 649 (p.P649L) in a conserved domain of the encoded protein. (J:38910)
• Inheritance: Recessive

Disease models

Expression

In Mice Carrying this Mutation:	1 assay results 1 RNA-Seq or microarray experiment(s)
In Structures Affected by this Mutation:	4 anatomical structure(s)

Find Mice (IMSR)

• Mouse strains and cell lines available from the International Mouse Strain Resource (IMSR)
• Carrying this Mutation: Mouse Strains: 1 strain available Cell Lines: 0 lines available
• Carrying any Cacna1a Mutation: 118 strains or lines available

Notes

Sudden arrests of movement (behavioral absence seizures) begin at about 3 weeks of age and are accompanied by abnormal bursts of bilaterally synchronous spike waves in electrocorticograms (EEG); they last about 0.3 to 10.0 seconds, occur hundreds of times per day, and continue throughout life (J:6154). Resemblance to human epileptic absence seizures suggests the use of these mutants in epilepsy research (J:1254). Prolonged paroxysmal depolarizing shifts in hippocampal pyramidal neurons of tottering mice occur in response to elevated extracellular potassium and are age-correlated with the appearance of seizures (J:1180). Genetically altered sensitivity to increased K+, however, is not the cause of the hyperexcitability of hippocampal neurons in mutant mice (J:15775). Stereotyped partial motor seizures begin at about 4 weeks of age and are accompanied by abnormal EEG activity; they last 20 to 30 minutes, occur once or twice a day, and persist throughout life (J:6154). The central nervous system appears normal by light microscopy (J:7519). There is no discernible cerebellar hypoplasia (J:15016). In fluorescent histochemistry studies Cacna1a^tg homozygous mice show a marked increase in number of noradrenergic fibers in the terminal fields innervated by locus ceruleus axons, the hippocampus, cerebellum, and dorsal lateral geniculate (J:6615). Treatment of neonatal mutant mice with 6-hydroxydopamine, which selectively causes degeneration of distal noradrenergic axons from the locus ceruleus, almost completely abolishes the ataxic and seizure symptoms and the abnormal EEG patterns (J:7519). These results suggest that the primary effect of Cacna1a^tg may be in the neurons of the locus ceruleus. However, there was no quantitative difference in tyrosine hydroxylase (TH) mRNA or protein in the locus ceruleus of Cacna1a^tg/Cacna1a^tg or Cacna1a^tg/Cacna1a^tg-la mice, whereas these mutants expressed high levels of TH mRNA and protein in cerebellar Purkinje cells (J:2495). Normal cerebellar Purkinje cells express TH transiently during development, but expression persists into adulthood in mutant mice (J:10927). Levels of oxidized glutathione are lowered in hippocampus and occipital cortex of Cacna1a^tg homozygotes, whereas reduced glutathione was lowered in the cerebellum (J:28460). The level of methionine-enkephalin, but not those of [?]-endorphin or dynorphin, was increased in several brain areas (J:633).

References

• Original: J:262 GREEN MC, et al., Tottering--a neuromusclar mutation in the mouse. And its linkage with oligosyndacylism. J Hered. 1962 Sep-Oct;53:233-7
• All: 70 reference(s)