These mice carry an ENU-induced allelic mutation of the Dst (Dystonin) gene resulting in ataxia.
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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 Dstdt-J/J (JR# 0211) have been performed to determine if NMF339 represents an allele of Dst (Dystonin). Four heterozygote matings (NMF339 x Dstdt-J/J, n=2; Dstdt-J/J) x NMF339, n=2) produced 8 mutants in a total of 30 progeny, suggesting that NMF339 indeed represents a new allele of Dstdt-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.
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 Name||dystonia musculorum 37, Jackson|
|Allele Type||Chemically induced (ENU)|
|Allele Synonym(s)||Dstnmf339; neuroscience mutagenesis facility, 339; NMF339|
|Gene Symbol and Name||Dst, dystonin|
|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.|