This spontaneous mutation of the dynamin 1 (Dnm1) gene displays ataxia, hearing impairment and seizures and may be useful in the study of epilepsy.
Wayne Frankel, JAX
The Fitful mutation is missense mutation resulting in an amino acid change in the middle domain of an alternatively spliced region.
Although protein is expressed, it does not efficiently assemble into dynamin complexes.
On the C57BL/6 background, mice homozygous for the semidominant, spontaneous mutation Fitful exhibit ataxia, hearing impairment, convulsive seizures and delayed growth. By post-natal day 12 (P12), mice can be distinguished from wildtype by an abnormal and uncoordinated stance and gait. Spontaneous tonic-clonic seizures begin by P14-16. Most homozygotes die by P18 as a result of lethal seizure or lack of nourishment due to physical weakening. Immunofluorescence microscopy of homozygote brains reveals smaller Purkinje cell dendritic trees than controls, which are characterized by a reduced dendritic arbor and degree of branching as well as spiny dendrites and a disorderly arrangement of soma. Heterozygous mice develop partial and generalized tonic-clonic seizures beginning at 2-3 months of age. In addition, they exhibit a reduced seizure threshold to electrical stimulus and a predisposition to kindled seizures. This mutant mouse strain may be useful in studies of epilepsy.
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
The Fitful (Ftfl) mutation arose spontaneously in the C57BL/6J inbred strain at The Jackson Laboratory in 2000. Determined to be a missense point mutation, this mutation results in an G to A substitution in exon 10, the first of two alternatively spliced regions. The mutation alters the corresponding amino acid from alanine to threonine at amino acid 408 affecting only the "ax" isoform sequences. Fitful was introgressed into FVB/NJ for 10 generations in the laboratory of Dr. Wayne Frankel. The strain was cryopreserved in 2010 at N10.
|Allele Type||Spontaneous (Modified isoform(s))|
|Gene Symbol and Name||Dnm1, dynamin 1|
|Strain of Origin||C57BL/6J|
|Molecular Note||A single change of a G-to-A in the first of two alternatively spliced regions results in an alanine to threonine substitution at amino acid 408 (p.A408T). This mutation only affects the Dnm1ax isoform sequences; the a exon is spliced out in the Dnm1bx forms, resulting all three Dnm1ax transcripts being altered.|
Most homozygotes die by P18 as a result of lethal seizure or lack of nourishment due to physical weakening.
When using the FVB.B6-Dnm1Ftfl/Frk mouse strain in a publication, please cite the originating article(s) and include JAX stock #005976 in your Materials and Methods section.
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