The pH of jimpy glia is increased: intracellular measurements using fluorescent laser cytometry.
The jimpy mutation lies in the gene which codes for myelin proteolipid protein, and the brains and spinal cords of jimpy mice contain little myelin and no measurable proteolipid protein. It has been thought that the mutation affected only the myelin forming oligodendroglial cells, but there is now considerable evidence that astroglia are also a target of the mutation since jimpy astrocytes exhibit a prominent gliosis along with defects in metabolism and proliferation. Because cell proliferation is associated with an increase in intracellular pH, we investigated whether the pH of jimpy glia was abnormal. Using a pH sensitive fluorescent dye and a laser cytometry system we measured the intracellular pH of individual cells in cultures derived from both jimpy and normal brains. The relative pH of flat astrocytes in jimpy cultures was higher than in normal cultures by an average of 0.24 pH units, and these increased values were evident 2-3 days after plating. At this in vitro age the cultures contain only a few oligodendrocytes, none of which express detectable proteolipid protein. The pH of the process-bearing cell population, which contains the oligodendrocytes as well as some astrocytes and presumptive glial precursors, was also increased but not until 7 days in culture. The finding that a mutation in the myelin proteolipid protein gene can alter the normal pH of astrocytes is quite unexpected since, as far as is known, astrocytes do not make proteolipid protein. These results and others discussed in this paper support the hypothesis that either proteolipid protein itself, or some other product of the gene, may have an important role in central nervous system development.
Knapp
P E
PE
Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201.
Booth
C S
CS
Skoff
R P
RP
D000818:Animals; D005434:Flow Cytometry; D005453:Fluorescence; D005456:Fluorescent Dyes; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D007834:Lasers; D008297:Male; D051379:Mice; D008816:Mice, Jimpy; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D009457:Neuroglia / Q000378:metabolism / Q000648:ultrastructure*; D009836:Oligodendroglia / Q000648:ultrastructure
D005456:Fluorescent Dyes; D009419:Nerve Tissue Proteins