| Primary Identifier | MGI:1856210 | Allele Type | Spontaneous |
| Attribute String | Not Specified | Gene | Cacna1a |
| Inheritance Mode | Recessive | Strain of Origin | AKR/J |
| Is Recombinase | false | Is Wild Type | false |
| description | Cacna1atg-la, leaner, recessive. The leaner mutation arose spontaneously in the AKR/J strain. Homozygotes are recognized at 8 to 10 days of age by ataxia, stiffness, and retarded motor activity. Adults are characterized by instability of the trunk, and hypertonia of trunk and limb muscles. Seizures have not been observed (J:28459). Heterozygous Cacna1atg-la/Cacna1atg mice show ataxia, stiffness, and retarded motor activity at 15 to 17 days of age. Within a few days they develop a wobbly gait and intermittent focal seizures that continue throughout life (J:5240). The cerebellum is reduced in size, particularly in the anterior region, in Cacna1atg-la homozygous mice (J:28459). There is loss of granule cells beginning at 10 days of age and loss of Purkinje and Golgi cells beginning after 1 month. Cell loss later slows but continues throughout life. Granule and Purkinje cells are more severely affected than Golgi cells and the anterior folia more severely affected than other parts of the cerebellum (J:6909). Heckroth and Abbott (J:20921) found loss of Purkinje cells from alternating sagittal zones of the cerebellum in Cacna1atg-la homozygotes. The cerebellum of Cacna1atg-la/Cacna1atg heterozygotes shows shrinkage and degenerative changes of the Purkinje cells (J:5240). The loss in cerebellar volume in these and in homozygous Cacna1atg mice is specific to the molecular layer, with no change in volume of the granule cell or white matter layers (J:22482). Many Cacna1atg-la homozygotes die at weaning time, but some survive and females may breed (J:28459). |
| molecularNote | This mutant allele comprises a G-to-A nucleotide substitution, changing the splice donor consensus sequence at the 5' end of intron 42 from G-gt to G-at. This abolishes or greatly reduces the efficiency of the splice site and results in aberrant transcripts that skip exon 42 or retain intron 42, both of wich are out-of-frame alterations. |
