Neural cell type-specific expression of QKI proteins is altered in quakingviable mutant mice

Abstract

qkl, a newly cloned gene lying immediately proximal to the deletion in the quakingviable mutation, is transcribed into three messages of 5, 6, and 7 kb. Antibodies raised to the unique carboxy peptides of the resulting QKl proteins reveal that, in the ferrous system, all three QKl proteins are expressed strongly in myelin-forming cells and also in astrocytes. Interestingly, individual isoforms show distinct intracellular distributions: QKl-6 and QKl-7 are localized to perikaryal cytoplasm, whereas QKl-5 invariably is restricted to the nucleus, consistent with the predicted role of QKl as an RNA-binding protein. In quakingviable mutants, which display severe dysmyelination, QKl-6 and QKl-7 are absent exclusively from myelin- forming cells. By contrast, QKl-5 is absent only in oligodendrocytes of severely affected tracts. These observations implicate QKl proteins as regulators of myelination and reveal key insights into the mechanisms of dysmyelination in the quakingviable mutant.