title: A new ENU-induced allele of mouse quaking causes severe CNS dysmyelination.
abstract: The mutant allelic series of the mouse quaking gene consists of the spontaneous quaking(viable) (qk(v)) allele, which is homozygous viable with a dysmyelination phenotype, and four ENU-induced alleles (qk(kt 1), qk(k2), qk(kt3/4), and qk(l-1)), which are homozygous embryonic lethal. Here we report the isolation of qk(e5), the first ENU-induced viable allele of quaking. Unlike qk(v)/qk(v), qk(e5)/qk(e5) animals have early-onset seizures, severe ataxia, and a dramatically reduced lifespan. Ultrastructural analysis of qk(e5)/qk(e5) brains reveals severe dysmyelination when compared with both wild-type and qk(v)/qk(v) brains. In addition, Calbindin detection in young adult qk(e5)/qk(e5) mice reveals Purkinje cell axonal swellings indicative of neurodegeneration , which is not seen in young adult qk(v)/qk(v) mice. Although the molecular defect in the qk(e5) allele is not evident by sequencing, protein expression studies show that qk(e5)/qk(e5) postnatal oligodendrocytes lack the QKI-6 and QKI-7 isoforms and have reduced QKI-5 levels. The oligodendrocyte developmental markers PDGF alpha R, NG 2, O4, CNP, and MBP are also present in the qk(e5)/qk(e5) postnatal brain although CNP and MBP levels are considerably reduced. Because the qk(v) allele is a large deletion that affects the expression of three genes, the new neurologic qk(e5) allele is an important addition to this allelic series.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, S413, Houston, Texas 77030, USA.
authors.forename: Janice K
authors.initials: JK
authors.lastname: Noveroske
authors.forename: Rebecca
authors.initials: R
authors.lastname: Hardy
authors.forename: Jason D
authors.initials: JD
authors.lastname: Dapper
authors.forename: Hannes
authors.initials: H
authors.lastname: Vogel
authors.forename: Monica J
authors.initials: MJ
authors.lastname: Justice
mesh_terms: D000483:Alleles; D000818:Animals; D015152:Blotting, Northern; D064026:Calbindins; D002490:Central Nervous System / Q000648:ultrastructure*; D003433:Crosses, Genetic; D017931:DNA Primers; D003711:Demyelinating Diseases / Q000235:genetics* / Q000473:pathology; D005038:Ethylnitrosourea; D007150:Immunohistochemistry; D051379:Mice; D008821:Mice, Quaking; D046529:Microscopy, Electron, Transmission; D016296:Mutagenesis; D010641:Phenotype; D016601:RNA-Binding Proteins / Q000235:genetics*; D064030:S100 Calcium Binding Protein G; D017422:Sequence Analysis, DNA
chemical_list: D064026:Calbindins; D017931:DNA Primers; C098217:Qk protein, mouse; D016601:RNA-Binding Proteins; D064030:S100 Calcium Binding Protein G; D005038:Ethylnitrosourea