DIFFERENCES IN THE RETINAL GABA SYSTEM AMONG CONTROL, SPASTIC MUTANT AND RETINAL DEGENERATION MUTANT MICE

Immunocytochemical methods were used to compare the GABA system in con trol mice and two mutant strains: spastic which has reduced glycine re ceptors and retinal degeneration mutant in which the photoreceptors de generate and reportedly have increased GABA and GAD levels. We found t hat the spastic mutant retina had reduced GABA-immunoreactivity (IR) i n the proximal retina, reduced staining for GAD-1440 in the OPL, and r educed GABA(A) receptor staining in the OPL, compared to control, The retinal degeneration mutant retinas had enhanced GABA-IR throughout th e retina, particularly in Muller cells, bipolar cells and IPL, and enh ancement of GABA(A) receptor staining in the OPL, compared to control. The distributions of GABA-IR, GAD-1440-IR and GABA(A) receptor-IR in retinas of spastic mutant mice that also expressed the retinal degener ation phenotype resembled those found in retinas of mice that expresse d only the retinal degeneration phenotype rather than those that expre ssed only the spastic mutation. No differences were observed among the conditions for GAD-65, GAD-67 or GABA-T, Our results with the spastic and retinal degeneration mutant mice demonstrate that attenuation in the glycinergic system and photoreceptor degeneration, respectively, i s accompanied by alterations in different aspects of the BABA system, giving impetus for caution in the interpretation of experiments involv ing genetic manipulation of complex phenotypes, (C) 1997 Elsevier Scie nce Ltd.