Phenotypic knockout of nerve growth factor in adult transgenic mice reveals severe deficits in basal forebrain cholinergic neurons, cell death in the spleen and skeletal muscle dystrophy
The disruption of the nerve growth factor (NGF) gene in trans-
genic mice leads to a lethal phenotype (Crowley et al., 1994)
and hinders the study of NGF functions in the adult. In this
study the phenotypic knockout of NGF in adult mice was
achieved by expressing transgenic anti-NGF antibodies, under
the control of the human cytomegalovirus promoter. In adult
mice, antibody levels are 2000-fold higher than in newborns.
Classical NGF targets, including sympathetic and sensory neu-
rons, are severely affected. In the CNS, basal forebrain and
hippocampal cholinergic neurons are not affected in the early
postnatal period, whereas they are greatly reduced in the adult
(55 and 62% reduction, respectively). Adult mice show a re-
duced ability in spatial learning behavioral tasks. Adult, but not
neonatal, transgenic mice further show a new phenotype at the
level of peripheral tissues, such as apoptosis in the spleen and
dystrophy of skeletal muscles. The analysis of this novel com-
prehensive transgenic model settles the controversial issue
regarding the NGF dependence of cholinergic neurons in adult
animals and reveals new NGF functions in adult non-neuronal
tissues. The results demonstrate that the decreased availability
of NGF in the adult causes phenotypic effects via processes
that are at least partially distinct from early developmental
effects of NGF deprivation
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