Elevated levels of the chemokine GRO-1 correlate with elevated oligodendrocyte progenitor proliferation in the jimpy mutant

The dysmyelinating mutant jimpy (jp) arises from a point mutation in the mo use gene encoding proteolipid protein and is characterized by severe dysmye lination attributable to oligodendrocyte death. This mutant was used to inv estigate the regulation of oligodendrocyte progenitor proliferation in the postnatal spinal cord. At postnatal day 18, jp spinal cord contained a thre e- to eightfold greater number of proliferating oligodendrocyte progenitor cells than did wild-type (wt) spinal cord. Increased proliferation in jp sp inal cord was accompanied by a twofold increase in the number of progenitor cells. Semiquantitative reverse transcriptase-PCR revealed no change in th e level of mRNA encoding the platelet-derived growth factor A, transforming growth factor-beta, or insulin-like growth factor-I, all of which have bee n implicated as regulators of proliferation and differentiation of oligoden drocyte progenitor cells. There was, however, a 17-fold increase in the lev el 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 reveale d elevated levels of GRO-1 in reactive astrocytes in jp spinal cord white m atter. In vitro studies indicated that extracts from jp spinal cord stimula ted oligodendrocyte progenitor proliferation. Furthermore, removal of GRO-1 from jp extracts by immunoprecipitation reduced the proliferation of proge nitor cells to a level similar to that achieved by wt extracts. These findi ngs suggest a novel mechanism by which proliferation of oligodendrocyte pro genitor cells is regulated in the postnatal spinal cord in response to insu lt.