The disruption of the nerve growth factor (NGF) gene in transgenic 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 neurons, 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 reduced 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 comprehensive 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.

Ruberti, F., Capsoni, S., Comparini, A., Di Daniel, E., Franzot, J., Gonfloni, S., et al. (2000). 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 JOURNAL OF NEUROSCIENCE, 20(7), 2589-2601.

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

GONFLONI, STEFANIA;
2000-04-01

Abstract

The disruption of the nerve growth factor (NGF) gene in transgenic 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 neurons, 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 reduced 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 comprehensive 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.
1-apr-2000
Pubblicato
Rilevanza internazionale
Abstract
Sì, ma tipo non specificato
Settore BIO/18 - GENETICA
English
Con Impact Factor ISI
Muscle, Skeletal; Male; Muscular Dystrophies; Cytomegalovirus; Female; Nerve Growth Factor; Phenotype; Cell Death; Mice, Knockout; Animals; Prosencephalon; Humans; Mice, Transgenic; Flow Cytometry; Apoptosis; Spleen; Gene Transfer Techniques; Mice; Gene Expression Regulation; Promoter Regions, Genetic; Spatial Behavior; Adult; Antibodies, Monoclonal; Immunoglobulin Light Chains
Ruberti, F., Capsoni, S., Comparini, A., Di Daniel, E., Franzot, J., Gonfloni, S., et al. (2000). 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 JOURNAL OF NEUROSCIENCE, 20(7), 2589-2601.
Ruberti, F; Capsoni, S; Comparini, A; Di Daniel, E; Franzot, J; Gonfloni, S; Rossi, G; Berardi, N; Cattaneo, A
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/9166
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