C57BL/6J-Dst^dt-37J/J

Stock number: 005560
Product name: dystonia musculorum(37J)
Strain synonyms: NMF339
Research areas: Neurobiology Research

Description

These mice carry an ENU-induced allelic mutation of the Dst (Dystonin) gene resulting in ataxia.

The Jackson Laboratory cannot guarantee that cryorecovery of strains from the discontinued NIH-funded Neuroscience Mutagenesis Facility (NMF) will be successful or that the anticipated phenotype or genotype will be obtained. The cryorecovery fee for this effort will not be refunded or prorated if the recovery is unsuccessful or is in any way unsatisfactory. Genotyping will be the responsibility of the Purchaser.

Detailed description

The mutants are small and their movement ability is severely limited. They move forward mainly by 'robbing' on their belly, since their front limbs are usually bent at the elbow, and their hind limbs lag behind. No muscle tonus is apparent in either front- or hind limbs upon gently pulling a limb, indicating flaccid paralysis of these limbs. A righting reflex is present only in rudimentary form, i.e. it may take a few seconds before the animal can righten itself from a back-lying position; when picked up by their tail, front- and hind limbs come together, the former are pulled backward, the latter move forward.

Because of phenotypic similarity to dystonia musculorum, complementation tests with Dst^dt-J/J (JR# 0211) have been performed to determine if NMF339 represents an allele of Dst (Dystonin). Four heterozygote matings (NMF339 x Dst^dt-J/J, n=2; Dst^dt-J/J) x NMF339, n=2) produced 8 mutants in a total of 30 progeny, suggesting that NMF339 indeed represents a new allele of Dst^dt-J.

Standard pathology work-up performed on three mutants at 19 (n=1) or 21 (n=2) days of age showed central chromatolysis in neurons of the brain stem and spinal cord, and dystrophic axons. Myelin degeneration, characterized by myelin figures in the cytoplasm of neurons was noted in the peripheral nerves; small muscle fibers and hypoplastic bone marrow (at 21 days of age) were also observed.

These mice are affected at a young age (average onset 2.8 weeks +/- 1; n=21), and the colony had to be maintained through ovarian transplants.

Development

This phenotypic deviant was generated by ethylnitrosourea (ENU) mutagenesis in C57BL/6J males (Stock No. 000664), in the Neuroscience Mutagenesis facility at The Jackson Laboratory. Mutagenized males were crossed to C57BL/6J females; G3 descendants of the mutagenized males were selected for neurological impairment.

Allele

Symbol: Dst^dt-37J
Name: dystonia musculorum 37, Jackson
MGI accession ID: MGI:3580065
Generation method: Chemically induced (ENU)
Marker symbol: Dst
Marker name: dystonin
Chromosome: 1
Strain of origin: C57BL/6J
Molecular note: This mutation was discovered in an ENU mutagenesis screen and was shown to be an allele of Dst by its failure to complement the dystonia musculorum Jackson mutation.