title: Dysmyelination with preservation of transverse bands in a long-lived allele of the quaking mouse.
abstract: The new mutant mouse shaking (shk) differs from other "myelin mutants" in having a more stable neurological impairment and a much longer lifespan. We have shown that transverse bands (TBs), the component of the paranodal junction (PNJ) that attaches the myelin sheath to the axon, are present in the shk central nervous system (CNS), in contrast to more severely affected mutants, in which TBs are absent or rare. We have proposed that TBs are the major determinant underlying shk neurological stability and longevity. Here we report that TBs are abundant not only in the shk CNS but also in its peripheral nervous system (PNS), which, as in other "myelin mutants", is not as severely dysmyelinated as the CNS but does display structural abnormalities likely to affect impulse propagation. In particular, myelin sheaths are thinner than normal, and some axonal segments lack myelin sheaths entirely. In addition, we establish that the shk mutation, previously localized to chromosome 17, is a quaking (qk) allele consisting of a 105-nucleotide insertion in the qk regulatory region that decreases qk transcription but does not extend to the Parkin and Parkin coregulated genes, which are affected in the qk allele. We conclude that: 1) dysmyelination is less severe in the shk PNS than in the CNS, but TBs, which are present in both locations, stabilize the PNJs and prevent the progressive neurological deficits seen in mutants lacking TBs; and 2) the insertional mutation in shk mice is sufficient to produce the characteristic neurological phenotype without involvement of the Parkin and Parkin coregulated genes.
authors.affiliation: Department of Neuroscience & Physiology, New York University School of Medicine, New York, New York, 10016.
authors.forename: Florence
authors.initials: F
authors.lastname: Chaverneff
authors.forename: Amanda
authors.initials: A
authors.lastname: Mierzwa
authors.forename: Michael
authors.initials: M
authors.lastname: Weinstock
authors.forename: Maren
authors.initials: M
authors.lastname: Ketcham
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lang
authors.forename: Jack
authors.initials: J
authors.lastname: Rosenbluth
mesh_terms: D000483:Alleles; D000818:Animals; D001369:Axons / Q000473:pathology / Q000502:physiology; D001921:Brain / Q000473:pathology; D003711:Demyelinating Diseases / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D008297:Male; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016254:Mutagenesis, Insertional; D009186:Myelin Sheath / Q000473:pathology* / Q000502:physiology; D009431:Neural Conduction; D009900:Optic Nerve / Q000473:pathology; D010641:Phenotype; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D012584:Sciatic Nerve / Q000473:pathology / Q000503:physiopathology; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology
chemical_list: C098217:Qk protein, mouse; D016601:RNA-Binding Proteins
keywords: autism; demyelination; multiple sclerosis; myelin; node of Ranvier; paranodal junction; schizophrenia