C57BL/6J-Dnm1^Ftfl/FrkJ

Stock number: 029988
Product name: fitful
Research areas: Neurobiology Research

Description

Mice homozygous for the Fitful (Ftfl) mutation in the dynamin 1 (Dnm1) gene demonstrate ataxia, hearing impairment, and seizures relevant to the study of epilepsy.

Detailed description

The semidominant Fitful (Ftfl) missense mutation arose spontaneously in the C57BL/6J inbred strain. A G to A substitution in exon 10 of the Dnm1 (dynamin 1) gene resulted in an amino acid change affecting an alternatively spliced region. Although protein is expressed, it does not efficiently assemble into dynamin complexes.

On the C57BL/6 background, homozygous mice 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 is useful in studies of epilepsy.

There are no significant phenotypic differences between this C57BL/6J background line and the FVB background line (see Stock No. 005976).

Development

Fitful (Ftfl), a semidominant missense mutation in the Dnm1 (dynamin) gene arose spontaneously in the C57BL/6J inbred strain at The Jackson Laboratory in 2000. A G to A substitution in exon 10 converts an alanine to a threonine at amino acid 408, affecting only the "ax" isoform sequences.

Allele

Symbol: Dnm1^Ftfl
Name: fitful
MGI accession ID: MGI:3033341
Generation method: Spontaneous
Attributes: Modified isoform(s)
Synonyms: Dyn1^ftfl
Marker symbol: Dnm1
Marker name: dynamin 1
Marker synonyms: DEE31; DEE31A; DEE31B; Dnm; EIEE31; Ftfl
Chromosome: 2
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.