Ae. Fray et al., Glutamine synthetase activity and expression are not affected by the development of motor neuronopathy in the G93A SOD-1/ALS mouse, MOL BRAIN R, 94(1-2), 2001, pp. 131-136
The expression and activity of the enzyme glutamine synthetase (GS) were ex
amined in the G93A/SOD-1 transgenic mouse model of progressive motor neuron
opathy to investigate the mechanisms underlying degeneration of the motor n
eurones. Clinical signs appeared in G93A/SOD-1 mice at around 90 days, with
severe spasticity and loss of self-righting reflex from 120 to 150 days of
age. GS expression was examined using western blotting in primary astrocyt
e cultures derived from newborn (P1-2) G93A/SOD-1 mice and their non-transg
enic littermates and in lower spinal cord from animals at 30, 60 and 90 day
s of age and disease end-stage (120-150 days). There were no differences in
the levels of GS expression in the transgenic mice compared to the unaffec
ted littermates at any of the disease stages examined. GS activity was meas
ured spectrophotometric ally in spinal cord extracts at these disease stage
s. There was a decrease in V-max at 60 days compared to 30 days in both gro
ups of mice (3.48 +/- 0.58 cf. 6.43 +/- 1.83 mmol/h/mg protein; non-transge
nic littermates), with GS activity highest at end-stage (9.38 +/- 0.71 mmol
/h/mg protein cf. 7.64 +/- 0.42 mmol/h/mg protein in littermates). Converse
ly, K-m was transiently increased at 60 days (2.53 +/- 0.26 mM cf. 1.32 +/-
0.20 in littermates), remaining within the range of 30 day measurements fr
om 90 days onwards. There were no differences in V-max or K-m values betwee
n the G93A/SOD-1 mice and their unaffected non-transgenic littermates at an
y of the disease stages examined. We conclude that there is no evidence tha
t a change in glutamine synthetase activity or expression contributes to th
e progressive neurodegeneration observed in the G93A/SOD-1 mice. (C) 2001 E
lsevier Science BY All rights reserved.