These mice carry two mutations, oligosyndactylism (Os) and leaner (Cacna1atg-la). Mice carrying leaner are characterized by ataxia, stiffness, and retarded motor activity while oligosyndactylism mice are characterized by fusion of digits.Read More +
Mice homozygous for the leaner spontaneous mutation (Cacna1atg-la) begin to show ataxia, stiffness, and retarded motor activity by 8 to 10 days of age. Many homozygous mutant mice die by weaning age, but some survive, and females may even breed. Homozygous mutant adults are characterized by instability of the trunk and hypertonia of the trunk and limb muscles. Seizures have not been observed. The cerebellum is reduced in size, particularly in the anterior region. There is loss of granule cells beginning at 10 days of age and loss of Purkinje and Golgi cells beginning after 1 month.
Leaner/tottering heterozygotes (Cacna1atg-la/Cacna1atg) 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 which continue throughout life. The cerebellum shows shrinkage and degenerative changes of the Purkinje cells.
The leaner allele (Cacna1atg-la) arose spontaneously in strain AKR/J at The Jackson Laboratory in 1960. It was backcrossed onto strain C57BL/6J reaching N10 in 1969. It was then crossed to the Sox18Ra/+ Os/+ Pt/+ strain probably on C57BL/6By. A very close linkage was found between leaner (Cacna1atg-la) and Os on Chromosome 8 and the balanced stock Os +/+ Cacna1atg-la was developed. It was sib mated by always selecting the Os phenotype and cryopreserved in 1985 by mating Os +/+ ? at N13 or N14F3 to C57BL/6J females.
|Allele Type||Spontaneous (Not Specified)|
|Allele Synonym(s)||Cacna1ala; Ln; tgla|
|Gene Symbol and Name||Cacna1a, calcium channel, voltage-dependent, P/Q type, alpha 1A subunit|
|Strain of Origin||AKR/J|
|General Note||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).|
|Molecular Note||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.|
|Allele Type||Radiation induced|
|Gene Symbol and Name||Os, oligosyndactylism|
|Strain of Origin||(101 x C3H)F1|
|General Note||Heterozygotes are affected on all four feet. Fusion usually occurs between the second and third digits and occasionally involves the fourth (J:13049). The muscles of the forearms and lower legs as well as of the feet show anomalous arrangements not necessarily correlated with the skeletal changes (J:12944). At 11 days of gestation the preaxial border of the limbs can be seen to be reduced (J:12942), and a histological examination at this time shows that there is a small amount of cellular degeneration in the preaxial part of the footplate mesoderm, leading to coalescence of the second and third digital rudiments (J:5107). Os /+ mice have a mild diabetes insipidus present at 5 weeks and increasing with age. In combination with one or more recessive modifying genes in the selected DI stock, Os/+ mice have a severe diabetes insipidus (J:12948). The cause of the diabetes is a 45% reduction in size of the kidneys with an 80% reduction in number of glomeruli. Compensatory hypertrophy of the nephrons is not sufficient to restore normal urine-concentrating ability (J:5127)(J:5128).|
|Molecular Note||The oligosyndactylism mutation is due to a chromosomal inversion that has breakpoints approximately 10 Mb apart. One breakpoint appears to reside in the Anapc10 gene, and an aberrant transcript consisting of part of Anapc10 and an unrelated sequence is expressed at low levels.|
When using the B6.Cg-Os +/+ Cacna1atg-la/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #000566 in your Materials and Methods section.
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