TY - JOUR T1 - Elevated Levels of the Chemokine GRO-1 Correlate with Elevated Oligodendrocyte Progenitor Proliferation in the<em>Jimpy</em> Mutant JF - The Journal of Neuroscience JO - J. Neurosci. SP - 2609 LP - 2617 DO - 10.1523/JNEUROSCI.20-07-02609.2000 VL - 20 IS - 7 AU - Qian Wu AU - Robert H. Miller AU - Richard M. Ransohoff AU - Shenandoah Robinson AU - Jie Bu AU - Akiko Nishiyama Y1 - 2000/04/01 UR - http://www.jneurosci.org/content/20/7/2609.abstract N2 - The dysmyelinating mutant jimpy(jp) arises from a point mutation in the mouse gene encoding proteolipid protein and is characterized by severe dysmyelination attributable to oligodendrocyte death. This mutant was used to investigate the regulation of oligodendrocyte progenitor proliferation in the postnatal spinal cord. At postnatal day 18,jp spinal cord contained a three- to eightfold greater number of proliferating oligodendrocyte progenitor cells than didwild-type (wt) spinal cord. Increased proliferation in jp spinal cord was accompanied by a twofold increase in the number of progenitor cells. Semiquantitative reverse transcriptase-PCR revealed no change in the level of mRNA encoding the platelet-derived growth factor A, transforming growth factor-β, or insulin-like growth factor-I, all of which have been implicated as regulators of proliferation and differentiation of oligodendrocyte progenitor cells. There was, however, a 17-fold increase in the level of mRNA encoding the chemokine GRO-1 and a 5- to 6-fold increase in GRO-1 protein in the jp spinal cord. Double immunofluorescence labeling revealed elevated levels of GRO-1 in reactive astrocytes in jp spinal cord white matter.In vitro studies indicated that extracts fromjp spinal cord stimulated oligodendrocyte progenitor proliferation. Furthermore, removal of GRO-1 from jpextracts by immunoprecipitation reduced the proliferation of progenitor cells to a level similar to that achieved by wtextracts. These findings suggest a novel mechanism by which proliferation of oligodendrocyte progenitor cells is regulated in the postnatal spinal cord in response to insult. ER -