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Cacna1atg
Spontaneous Allele Detail
Summary
Symbol: Cacna1atg
Name: calcium channel, voltage-dependent, P/Q type, alpha 1A subunit; tottering
MGI ID: MGI:1856209
Synonyms: alpha1Atg, tg
Gene: Cacna1a  Location: Chr8:85065268-85366875 bp, + strand  Genetic Position: Chr8, 40.95 cM
Alliance: Cacna1atg page
Mutation
origin
Strain of Origin:  DBA/2J
Mutation
description
Allele Type:    Spontaneous (Not Specified)
Mutation:    Single point mutation
 
Mutation detailsA 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
Phenotypes
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View phenotypes and curated references for all genotypes (concatenated display).
Disease models
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Expression
In Mice Carrying this Mutation: 1 assay results
In Structures Affected by this Mutation: 4 anatomical structures
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:  85 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 Cacna1atg 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 Cacna1atg 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 Cacna1atg/Cacna1atg or Cacna1atg/Cacna1atg-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 Cacna1atg 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:  69 reference(s)

Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
11/15/2022
MGI 6.22
The Jackson Laboratory