QUANTITATIVE IMMUNOCYTOCHEMICAL ANALYSIS OF THE SPINAL-CORD IN G86R SUPEROXIDE-DISMUTASE TRANSGENIC MICE - NEUROCHEMICAL CORRELATES OF SELECTIVE VULNERABILITY

Transgenic mice with a G86R mutation in the mouse superoxide dismutase (SOD-1) gene, which corresponds to a mutation that has been observed in familial amyotrophic lateral sclerosis (ALS), display progressive l oss of motor function and provide a valuable model of ALS. The patholo gy in the spinal cords of these mice was evaluated to determine whethe r there are chemically identified populations of neurons that are eith er highly vulnerable or resistant to degeneration. Qualitatively, ther e were phosphorylated neurofilament protein (NFP)-immunoreactive inclu sions and a pronounced loss of motoneurons in the ventral horn of the spinal cord without the presence of vacuoles that has been reported in other SOD-1 transgenic mice. Neuron counts from SOD-1 and control spi nal cords revealed that the percentage loss of NFP-, choline acetyltra nsferase (ChAT)-, and calretinin (CR)-immunoreactive neurons was great er than the percentage loss of total neurons, suggesting that these ne uronal groups are particularly vulnerable in SOD-1 transgenic mice. In contrast, calbindin-containing neurons did not degenerate significant ly and represent a protected population of neurons. Quantitative doubl e-labeling experiments suggested that the vulnerability of ChAT- and C R-immunoreactive neurons was due primarily to the presence of NFP with in a subset of these neurons, which degenerated preferentially to ChAT - and CR-immunoreactive neurons that did not colocalize with NFP. Our findings suggest that NFP, which has been demonstrated previously to b e involved mechanistically in motoneuron degeneration, may also be imp ortant in the mechanism of degeneration that is initiated by the SOD-1 mutation. (C) 1996 Wiley-Liss, Inc.