The mutant allelic series of the mouse
quaking gene consists of the spontaneous
quakingviable (
qkv) allele, which is homozygous viable with a dysmyelination phenotype, and four ENU-induced alleles (
qkkt1,
qkk2,
qkkt3/4, and
qkl-1), which are homozygous embryonic lethal. Here we report the isolation of
qke5, the first ENU-induced viable allele of
quaking. Unlike
qkv/
qkv,
qke5/
qke5 animals have early-onset seizures, severe ataxia, and a dramatically reduced lifespan. Ultrastructural analysis of
qke5/
qke5 brains reveals severe dysmyelination when compared with both wild-type and
qkv/
qkv brains. In addition, Calbindin detection in young adult
qke5/
qke5 mice reveals Purkinje cell axonal swellings indicative of neurodegeneration , which is not seen in young adult
qkv/
qkv mice. Although the molecular defect in the
qke5 allele is not evident by sequencing, protein expression studies show that
qke5/
qke5 postnatal oligodendrocytes lack the QKI-6 and QKI-7 isoforms and have reduced QKI-5 levels. The oligodendrocyte developmental
markers PDGFαR, NG2, O4, CNP, and MBP are also present in the
qke5/
qke5 postnatal brain although CNP and MBP levels are considerably reduced. Because the
qkv allele is a large deletion that affects the expression of three genes, the new neurologic
qke5 allele is an important addition to this allelic series.
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